Paimionjoen säännöstelyn kehittäminen : Paimionjoen vesistön yläosan hydraulinen mallinnus HEC-RAS ohjelmistolla

Paimionjoen järviketjulla vedenpinnan ja virtaaman vaihteluiden on koettu aiheuttavan haittaa vesistön käytölle ja tilalle. Kevätkuopan alhaisuus ja takaisinvirtaus Painiojärveen ovat suurimmat ongelmat. Turun kaupungin vesiliikelaitoksen Halisten vesilaitoksen tuotantotoiminnan loppuminen antaa uusia mahdollisuuksia Paimionjoen järviketjun säännöstelyyn, koska järvien rooli Turun seudun raakaveden varastona muuttuu. Tässä raportissa tarkastellaan Paimionjoen yläosasta tehtyä hydraulista mallinnusta, jossa on testattu erilaisia pato- ja juoksutusvaihtoehtoja Paimionjoen järviketjulla sekä niiden vaikutuksia vedenkorkeuksiin ja virtaamiin. Myös ruoppausta Karjakosken ja Hovirinnankosken väliselle osuudelle on käsitelty lyhyesti. Erilaisista skenaarioista on tehty alustavat vaikutusarviot. Mallinnusten perusteella suurempi tai aikaistettu juoksutus pienentää takai-sin-virtausta, muttei estä sitä kokonaan. Juoksutusta ei kuitenkaan välttämättä pysty lisäämään miten haluaa, koska juoksutuksen suuruus riippuu Hovirinnankoskenpadon alapuolisesta vedenpinnankorkeudesta. Ruoppaamalla Hovirinnankosken ja Karjakosken välistä osuutta Hovirinnankosken alapuolista vedenpintaa voisi saada alennettua ja osuuden vetokykyä parannettua sekä tulvimisherkkyyttä pienennettyä. Kevätkuopan pienennys vähentää takaisinvirtausta ja on myös järvien ekosysteemeille hyväksi. Tulvariskin kasvu tulee kuitenkin ottaa huomioon. Painionjärvi toimii tulvatilanteissa paisumisaltaana. Kaikenlainen takaisinvirtaaman estäminen tai pienentäminen johtaa suurempiin juoksutuksiin Hovirinnankoskella tai/ja järviketjun kasvaneisiin vedenkorkeuksiin ja mahdollisesti tulviin. Erilaisten tulvakorkeuksien mahdolliset riskirajat ja vahingot tulee selvittää, jos tulvariskiä kasvatetaan.

Nanoclustering augmentation : a novel mechanism of Ras activation in cancer

Proteins of the Ras family are central regulators of crucial cellular processes, such as proliferation, differentiation and apoptosis. Their importance is emphasized in cancer, in which the isoforms H-ras, N-ras and K-ras are misregulated by mutations in approximately 20 – 30 % of cases. Thus, they represent major cancer oncogenes and one of the most important targets for cancer drug development. Ras proteins are small GTPases, which cycle between the GTP-bound active and GDP-bound inactive state. Despite the tremendous research conducted in the last three decades, many fundamental properties of Ras proteins remain poorly understood. For instance, although new concepts have recently emerged, the understanding of Ras behavior in its native environment, the membrane, is still largely missing. On the membrane Ras organizes into nanoscale clusters, also called nanoclusters. They differ between isoforms, but also between activation states of Ras. It is considered that nanoclusters represent the basic Ras signaling units. Recently, it was demonstrated that on the membrane Ras adopts distinct conformations, the so-called orientations, which are dependent on the Ras activations state. The membrane-orientation of H-ras is stabilized by the helix α4 and the C-terminal hypervariable region (hvr). The novel switch III region was proposed to be involved in mediating the change between different H-ras orientations. When the regions involved in this mechanism are mutated, H-ras activity is changed by an unknown mechanism. This thesis has explained the connection between the change of Ras orientation on the membrane and Ras activity. We demonstrated that H-ras orientation mutants exhibit altered diffusion properties on the membrane, which reflect the changes in their nanoclustering. The altered nanoclustering consequently rules the activity of the mutants. Moreover, we demonstrated that specific cancer-related mutations, affecting the switch III region of different Ras isoforms, exhibit increased nanoclustering, which consequently leads to stronger Ras signaling and tumorigenicity. Thus, we have discovered nanoclustering increase as a novel mechanism of Ras activity modulation in cancer. The molecular architecture of complexes formed on the membrane upon Ras activation is another poorly understood property of Ras. The following work has provided novel details on the regulation of Ras nanoclustering by a known H-ras-GTP nanoclustering stabilizer galectin-1 (Gal-1). Our study demonstrated that Gal-1 is not able to bind Ras directly, as it was previously proposed. Instead, its effect on H-ras-GTP nanoclustering is indirect, through binding of the effector proteins. Collectively, our findings represent valuable novel insights in the behavior of Ras, which will help the future research to eventually develop new strategies to successfully target Ras in cancer.

Role and Function of c-Jun Protein Complex in Cancer Cell Behavior

Transcription factors play a crucial role in the regulation of cell behavior by modulating gene expression profiles. Previous studies have described a dual role for the AP-1 family transcription factor c-Jun in the regulation of cellular fate. In various cell types weak and transient activations of c-Jun N-terminal kinase (JNK) and c-Jun appear to contribute to proliferation and survival, whereas strong and prolonged activation of JNK and c-Jun result in apoptosis. These opposite roles played by c-Jun are cell type specific and the molecular mechanisms defining these antonymous c-Jun-mediated responses remain incompletely understood. c-Jun activity in transformed cells is regulated by signalling cascades downstream of oncoproteins such as Ras and Raf. In addition, the pro-proliferative role and the survival promoting function for c-Jun has been described in various cancer models. Furthermore, c-Jun was described to be overexpressed in different cancer types. However, the molecular mechanisms by which c-Jun exerts these oncogenic functions are not all clearly established. Therefore it is of primary interest to further identify molecular mechanisms and functions for c-Jun in cancer. Regulation of gene expression is tightly dependent on accurate protein-protein interactions. Therefore, co-factors for c-Jun may define the functions for c-Jun in cancer. Identification of protein-protein interactions promoting cancer may provide novel possibilities for cancer treatment. In this study, we show that DNA topoisomerase I (TopoI) is a transcriptional co-factor for c-Jun. Moreover, c-Jun and TopoI together promote expression of epidermal growth factor receptor (EGFR) in cancer cells. We also show that the clinically used TopoI inhibitor topotecan reduces EGFR expression. Importantly, the effect of TopoI on EGFR transcription was shown to depend on c-Jun as Jun-/- cells or cells treated with JNK inhibitor SP600125 are resistant to topotecan treatment both in regulation of EGFR expression and cell proliferation. Moreover, c-Jun regulates the nucleolar localization and the function of the ribonucleic acid (RNA) helicase DDX21, a previously identified member of c-Jun protein complex. In addition, c-Jun stimulates rRNA processing by supporting DDX21 rRNA binding. Finally, this study characterizes a DDX21 dependent expression of cyclin dependent kinase (Cdk) 6, a correlation of DDX21 expression with prostate cancer progression and a substrate binding dependency of DDX21 nucleolar localization in prostate cancer cells. Taken together, the results of this study validate the c-Jun-TopoI interaction and precise the c-Jun-DDX21 interaction. Moreover, these results show the importance for protein-protein interaction in the regulation of their cellular functions in cancer cell behavior. Finally, the results presented here disclose new exciting therapeutic opportunities for cancer treatment.

Tautomerism and Fragmentation of Biologically Active Hetero Atom (O, N)-Containing Acyclic and Cyclic Compounds Under Electron Ionization

In this thesis a total of 86 compounds containing the hetero atoms oxygen and nitrogen were studied under electron ionization mass spectrometry (EIMS). These compounds are biologically active and were synthesized by various research groups. The main attention of this study was paid on the fragmentations related to different tautomeric forms of 2- phenacylpyridines, 2-phenacylquinolines, 8-aryl-3,4-dioxo-2H,8H-6,7-dihydroimidazo- [2,1-c][1,2,4]triazines and aryl- and benzyl-substituted 2,3-dihydroimidazo[1,2-a]pyrimidine-5,7-(1H,6H)-diones. Also regio/stereospecific effects on fragmentations of pyrrolo- and isoindoloquinazolinones and naphthoxazine, naphthpyrrolo-oxazinone and naphthoxazino-benzoxazine derivatives were screened. Results were compared with NMR data, when available. The first part of thesis consists of theory and literature review of different types of tautomerism and fragmentation mechanisms in EIMS. The effects of tautomerism in biological systems are also briefly reviewed. In the second part of the thesis the own results of the author, based on six publications,are discussed. For 2-phenacylpyridines and 2-phenacylquinolines the correlation of different Hammett substituent constants to the relative abundances (RA) or total ion currents (% TIC) of selected ions were investigated. Although it was not possible to assign most of the ions formed unambiguously to the different tautomers, the linear fits of their RAs and % TICs can be related to changing contributions of different tautomeric forms. For dioxoimidazotriazines and imidazopyrimidinediones the effects of substituents were rather weak. The fragmentations were also found useful for obtaining structural information. Some stereoisomeric pairs of pyrrolo- and isoindoloquinazolines and regiomeric pairs of naphtoxazine derivatives showed clear differences in thir mass spectra. Some mechanisms are suggested for their fragmentations.

Therapeutic Properties of Superoxide Dismutase 3 and Mesenchymal Stromal Cells in Peripheral Ischemia

The aim of this study was to characterize the cellular mechanisms leading to the beneficial effect of anti-oxidative gene therapy and pro-angiogenic stem cell therapy in acute peripheral ischemia. Post-ischemic events aim to re-establish tissue blood perfusion, to clear cellular debris, and to regenerate lost tissue by differentiation of satellite cells into myoblasts. Although leukocytes have an essential role in clearing cellular debris and promoting angiogenesis, they also contribute to tissue injury through excessive ROS production. First, we investigated the therapeutic properties of extracellular superoxide dismutase (SOD3) gene transfer. SOD3 was shown to reduce oxidative stress, to normalize glucose metabolism, and to enhance cell proliferation in the ischemic muscle. Analysis of the mitogenic Ras-Erk1/2 pathway showed SOD3 mediated induction offering a plausible explanation for enhanced cell proliferation. In addition, SOD3 reduced NF-κB activity by enhancing IκBα expression thus leading to reduced expression of inflammatory cytokines and adhesion molecules with consequent reduction in macrophage infiltration. Secondly, we sought to determine the fate and the effect of locally transplanted mesenchymal stem/stromal cells (MSCs) in acute ischemia. We showed that a vast majority of the transplanted cells are cleared from the injury site within 24 hours after local transplantation. Despite rapid clearance, transplantation was able to temporarily promote angiogenesis and cell proliferation in the muscle. Lack of graft-derived growth factor expression suggests other than secretory function to mediate this observed effect. In conclusion, both SOD3 and MSCs could be utilized to alleviate peripheral ischemia induced tissue injury. We have described a previously unidentified growth regulatory role for SOD3, and suggest a novel mechanism whereby transplanted MSCs enhance the reparative potential of the recipient tissue through physical contacts.

Anchor or Accelerate – A Study on Cancer Cell Adhesion and Motility

Cell migration and adhesion to the extracellular matrix (ECM) are crucial in many biological and pathological processes such as morphogenesis, tissue repair, inflammatory responses, survival, and cancer. Cell-matrix adhesion is mediated by the integrin family of transmembrane receptors, which not only anchor cells to their surroundings, but also transmit bidirectional signalling at the cell surface and couple the ECM to the cytoskeleton. Another group of adhesion receptors are the syndecan proteoglycans, which engage the ECM and possess signalling activity in response to a variety of ligands. Cell migration is a complex process that requires spatial and temporal coordination of adhesion, cell contractility, intracellular traffic of integrins, and matrix turnover by matrix metalloproteinases (MMPs). Thus, integrins and syndecans, as well as MMPs, play essential roles in cancer cell migration and invasion. The understanding of the cooperation of syndecans and integrins was broadened in this thesis study. The results reveal that syndecan-1 functions in concert with 21 integrin in cell adhesion to collagen, whereas syndecan-4 is essential in 21 integrin-mediated matrix contraction. Finally, oncogenic K-Ras was shown to regulate 21 integrin, membrane-type 1 MMP, and syndecan-1 and -4 expression and their cooperation in cell invasion. Epithelial-mesenchymal transition (EMT) is fundamental during embryogenesis and organ development. Activation of EMT processes, including the upregulation of mesenchymal intermediate filament protein vimentin, has also been implicated in the acquisition of a malignant phenotype by epithelial cancer cells. Members of the protein kinase C (PKC) superfamily are involved in cell migration and various integrindependent cellular functions. One aim of this work was to shed light on the role of vimentin in the regulation of integrin traffic and cell motility. In addition, the mechanism by which vimentin participates in EMT was investigated. The results show that integrin recycling and motility are dependent on the PKC–mediated phosphorylation of vimentin. In addition, vimentin was found to be a positive regulator of EMT and regulate the expression of several migratory genes. Specifically, vimentin governs the expression of receptor tyrosine kinase Axl, which is implicated in tumour growth and metastasis. Taken together, the findings described in this thesis reveal novel aspects of the complex interplay between distinct cellular components: integrins, syndecans, and the vimentin cytoskeleton, which all contribute to the regulation of human cancer cell adhesion, migration, and invasion.

Pluralité et fluidité antinormatives : étude sur les transgressions sexuelles dans l’oeuvre romanesque de Marguerite Yourcenar

Avhandlingen är en studie i kön, genus och sexualitet i den franska författarinnan Marguerite Yourcenars romaner. Undersökningen utgår från ett queer-teoretiskt perspektiv och har som syfte att belysa de olika sätt på vilka Yourcenars texter uttrycker ett ifrågasättande av och ett överskridande av normer beträffande kön, manlighet och kvinnlighet, samt sexuella kategorier. Det tudelade könssystemet (man/kvinna) och motsättningen mellan heterosexualitet och homosexualitet ses som förenklade sociala konstruktioner som inte motsvarar den mångfasetterade verklighet som avbildas i texterna. Mångfald, flyktighet och gränsöverskridande är nyckelord i undersökningen. I avhandlingen granskas snart när alla Yourcenars romaner samt en novell i form av separata läsningar, för att ge en så heltäckande bild som möjligt av hur problematiken behandlas i hennes produktion. Således belyses särarten hos varje verk och det är även möjligt att uppmärksamma den utveckling som skett under karriärens gång. Kön och sexualitet diskuteras separat i enlighet med Gayle Rubins och Eve Sedgwicks tes att sexualitetsforskning och genusstudier inte bör sammanblandas: sexualitet är ett så komplext fenomen att kön och genus är otillräckliga analysverktyg för en seriös och djuplodande diskussion. Genom att lyfta fram olika exempel på figurer i Yourcenars romaner som implicit eller explicit tar avstånd ifrån en klar indelning i män och kvinnor, respektive manlighet och kvinnlighet, påvisas att tanken att det existerar två olika biologiska kön systematiskt tillbakavisas. Diskussionen om sexualitetstemat koncentrerar sig på förhållandet mellan homo-och heterosexualitet, men betonar även hur temat anknyter till andra centrala teman, såsom religion och ras. Bilden av homosexualitet ändrar från en text till en annan, vilket illusterar att en skarp motsättning mellan homo- och heterosexualitet är ohållbar.

D’abord, ensuite, enfin et 0, De plus: Organisation textuelle par des séries linéaires dans les articles de recherche

The study examines the signalling of text organisation in research articles (RA) in French. The work concentrates on a particular type of organisation provided by text sequences, i.e. structures organising text to items of which at least some are signalled by markers of addition or order: First… 0… The third point… In addition… / Premièrement… 0… Le troisième point… De plus… By indicating the way the text is organised, these structures guide the reader in the reading process so that he doesn’t need to interpret the text structure himself. The aim of the work is to study factors affecting the marking of text sequences. Why is their structure sometimes signalled explicitly by markers such as secondly, whereas in other places such markers are not used? The corpus is manually XML-annotated and consists of 90 RAs (~800 000 words) in French from the fields of linguistics, education and history. The analysis highlights several factors affecting the marking of text sequences. First, exact markers (such as fist ) seem to be more frequent in sequences where all the items are explicitly signalled by a marker, whereas additive markers (such as moreover) are used in sequences with both explicitly signalled and unmarked items. The marking of explicitly signalled sequences seems thus to be precise and even repetitive, whereas the signalling of sequences with unmarked items is altogether more vague. Second, the marking of text sequences seems to depend on the length of the text. The longer the text segment, the more vague the marking. Additive markers and unmarked items are more frequent in longer sequences possibly covering several pages, whereas shorter sequences are often signalled explicitly by exact markers. Also the marker types vary according to the sequence length. Anaphoric expressions, such as first, are fairly close to their referents and are used in short sequences, connectors, such as secondly, are frequently used in sequences of intermediate length, whereas the longest sequences are often signalled by constructions composed of an ordinal and a noun acting as a subject of the sentence: The first item is… Finally, the marking of text organisation depends also on the discipline the RA belongs to. In linguistics, the marking is fairly frequent and precise; exact markers such as second are the most used, and structures with unmarked items are less common. Similarly, the marking is fairly frequent in education. In this field, however, it is also less precise than in linguistics, with frequent unmarked items and additive markers. History, on the other hand, is characterised by less frequent marking. In addition, when used, the marking in this field is also less precise and less explicit.

Segregation of powder mixtures in silos with particular reference to dry mineral-based construction materials

Segregering eller segregation är ett fenomen som kan förekomma inom olika områden av samhället. Inom samhällsvetenskaperna kan segregering definieras som det rumsliga åtskiljandet av befolkningsgrupper på urval av ras eller etniskt ursprung, kön, social härkomst, religion, ålder, yrke, osv. Segregering av befolkningsgrupper sker ofta mer eller mindre frivilligt och är motsatsen till integration. Inom partikelteknologi definieras segregering oftast som det rumsliga åtskiljandet av beståndsdelarna i en blandning av olika partiklar. Segregering sker då på urval av bl.a. partiklarnas storlek, densitet, form, elektrostatiska eller mekaniska egenskaper, och kan beskrivas som motsatsen till blandning. Segregeringsmekanismer används för att förklara hur och varför en partikelblandning segregerar samt vad slutresultatet i form av den rumsliga fördelningen av partiklarna blir till följd av att blandningen utsetts för en viss behandling. I denna avhandling har segregering av partikelblandningar och speciellt torra mineralbaserade byggmaterial (t.ex. murbruk) till följd av lagring i siloer studerats. Vid industriell produktion av mineralbaserade byggmaterial används siloer för korttidslagring av slutprodukterna precis innan förpackning. Segregering leder till kraftiga variationer i sammansättningen för partikelströmmen ut ur silon, vilket gör att slutprodukterna inte uppfyller kvalitetskraven och kan därmed inte säljas till kunder. Detta leder till arbetsam och dyr bearbetning (återcirkulation) av produkterna med påföljder för produktionsekonomin samt hållbara utvecklingen. I avhandlingen identifierades de väsentligaste segregeringsmekanismerna för torra mineralbaserade byggmaterial i siloer. Dessutom klargjordes effekterna av materialegenskaper, processbetingelser och siloparametrar. Slutligen behandlas möjliga åtgärder för minskning av partikelsegregering i siloer samt tillämpning av matematiska metoder för simulering av partikelflöden med hjälp av datorer.

The Roots of Neurofibromas in Neurofibromatosis 1 — A Question of Multipotency, Differentiation and Hiding

Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome that affects about 1 in 3500 individuals worldwide. NF1 is caused by mutations in the NF1 gene that encodes the tumor suppressor protein neurofibromin, an inactivator of the Ras oncogene. The hallmarks of NF1 include pigmentary lesions of the skin, Lisch nodules of the iris and cutaneous neurofibromas. Cutaneous neurofibromas are benign tumors composed of all the cell types of normal peripheral nerve. The traditional view of neurofibroma development has been that cutaneous neurofibromas arise from the disruption of the small nerve tributaries of the skin and subsequent proliferation of the resident cells. The second hit mutation in the NF1 gene has been considered as a prerequisite for neurofibroma development. The second hit is detectable in a subpopulation of primary Schwann cells cultured from neurofibromas. This thesis challenges the traditional concept of neurofibroma development. The results show that cutaneous neurofibromas are intimately associated with hair follicular structures and contain multipotent precursor cells (NFPs), suggesting that neurofibromas may arise from the multipotent cells which reside in hair follicles. Furthermore, this study presents that neurofibroma-derived Schwann cells that harbor bi-allelic inactivation in the NF1 gene express HLA class II genes and may act as nonprofessional antigen presenting cells. The CD4- and FoxP3-positive cells detected in cutaneous neurofibromas suggest that these cells may represent regulatory T cells (Tregs) which interact with HLA II –positive cells and aid the tumor cells in hiding from the immune system and are thus mediators of immune tolerance. This thesis also investigated neurofibroma development in the oral cavity and the use of different biomarkers to characterize cellular differentiation in neurofibromas. The results revealed that oral neurofibromas are not rare, but they usually appear as solitary lesions contrary to multiple cutaneous neurofibromas and present high heterogeneity within and between tumors. The use of class III beta-tubulin as a marker for neuronal differentiation led to an unexpected finding showing that multiple cell types express class III beta-tubulin during mitosis. The increased understanding of the multipotency of tumor cells, cellular differentiation and ability to hide from immune system will aid in the development of future treatments. Specifically, targeting Tregs in NF1 patients could provide a novel therapeutic approach to interfere with the development of neurofibromas.

Long live! : South African HIV-activism, knowledge and power

Då aktivister i den sydafrikanska organisationen Treatment Action Campaign - TAC- demonstrerar för tillgång till bromsmediciner för den fattiga delen av världen, iklädda T-skjortor med texten "HIV-POSITIV", är de offer samtidigt som de är globala aktörer för en rättvisare värld. Denna typ av aktivism, och särskilt mobiliseringen av kvinnor som lever med hiv och kämpar för tillgång till bromsmediciner, utmanar aktuell, hälso- och hiv-forskning. Vidare kastar hiv-aktivismen ljus på globaliseringens effekter på sjukdom och hälsa. TAC är en hälsorörelse som fokuserar på hiv på såväl ett personligt, nationellt som globalt plan. Genom sitt breda perspektiv förskjuter TAC frågan om hiv från att handla om individuell sjukdom till att beröra ett brett spektrum av politiska frågor. Studien "Long Live! HIV-aktivism, knowledge and power", som grundar sig på ett rikt etnografisk material insamlat i Sydafrika under åren 200-2006, visar hur hiv-aktivisterna utmanar dikotomier mellan socialt och medicinskt, mellan behandling och prevention samt mellan aktör och offer. I TAC:s arbete dekonstrueras också de ofta skarpa konstrasterna mellan expert- och lekmannakunskap, eftersom organisationen belyser hur läkare, patienter och aktivister kan samarbeta för en fungerande hälsovård. Studien granskar hur TAC-aktivister, som lever med hiv, agerar som globala aktörer i sitt arbete för förändring. Studien visar vidare hur TAC-aktivister utmanar hur hiv-prevention och -behandling sätts i motsatsförhållande till varandra och hävdar att man inte kan ha det ena utan det andra. Man kan säga att aktivisternas kritik av hälsopolitik synliggör hur teorier om hälsa och sjukdom, måste ta i beaktande det komplexa förhållandet mellan kön, ras, klass och globala maktstrukturer.

Integrins in Tumorigenesis and Cancer Cell Invasion

The integrin family of transmembrane receptors are important for cell-matrix adhesion and signal transmission to the interior of the cell. Integrins are essential for many physiological processes and defective integrin function can consequently result in a multitude of diseases, including cancer. Integrin traffic is needed for completion of cytokinesis and cell division failure has been proposed to be an early event in the formation of chromosomally aberrant and transformed cells. Impaired integrin traffic and changes in integrin expression are known to promote invasion of malignant cells. However, the direct roles of impaired integrin traffic in tumorigenesis and increased integrin expression in oncogene driven invasion have not been examined. In this study we have investigated both of these aspects. We found that cells with reduced integrin endocytosis become binucleate and subsequently aneuploid. These aneuploid cells display characteristics of transformed cells; they are anchorage-independent, resistant to apoptosis and invasive in vitro. Importantly, subcutaneous injection of the aneuploid cells into athymic nude mice produced highly malignant tumors. Through gene expression profiling and analysis of integrin-triggered signaling pathways we have identified several molecules involved in the malignancy of these cells, including Src kinase and the transcription factor Twist2. Thus, even though chromosomal aberrations are associated with reduced cell fitness, we show that aneuploidy can facilitate tumor evolution and selection of transformed cells. Invasion and metastasis are the primary reason for deaths caused by cancer and the molecular pathways responsible for invasion are therefore attractive targets in cancer therapy. In addition to integrins, another major family of adhesion receptors are the proteoglycans syndecans. Integrins and syndecans are known to signal in a synergistic manner in controlling cell adhesion on 2D matrixes. Here we explored the role of syndecans as α2β1 integrin co-receptors in 3D collagen. We show that in breast cancer cells harbouring mutant K-Ras, increased levels of integrins, their co-receptors syndecans and matrix cleaving proteases are necessary for the invasive phenotype of these cells. Together, these findings increase our knowledge of the complicated changes that occur during tumorigenesis and the pathways that control the ability of cancer cells to invade and metastasize.