{"entity": "researcher", "timestamp": "2026-09-26T23:33:08.258Z", "family": "Rubin", "given": "Kristofer", "initials": "K", "orcid": "0000-0003-2789-6276", "affiliations": ["Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, BMC Box 582, SE-751 23, Uppsala, Sweden. kristofer.rubin@imbim.uu.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/60f2a0d933bf4bff95ef57efde91ac15.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/60f2a0d933bf4bff95ef57efde91ac15"}}, "publications": [{"entity": "publication", "iuid": "53bf58120834410db8fda089f739939b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/53bf58120834410db8fda089f739939b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/53bf58120834410db8fda089f739939b"}}, "title": "Inhibition of integrin \u03b1V\u03b26 changes fibril thickness of stromal collagen in experimental carcinomas.", "authors": [{"family": "Olof Olsson", "given": "P", "initials": "P"}, {"family": "Gustafsson", "given": "Renata", "initials": "R"}, {"family": "Salnikov", "given": "Alexei V", "initials": "AV"}, {"family": "G\u00f6the", "given": "Maria", "initials": "M"}, {"family": "Zeller", "given": "Kathrin S", "initials": "KS"}, {"family": "Friman", "given": "Tomas", "initials": "T"}, {"family": "Baldetorp", "given": "Bo", "initials": "B"}, {"family": "Koopman", "given": "Louise A", "initials": "LA"}, {"family": "Weinreb", "given": "Paul H", "initials": "PH"}, {"family": "Violette", "given": "Shelia M", "initials": "SM"}, {"family": "Kalamajski", "given": "Sebastian", "initials": "S"}, {"family": "Heldin", "given": "Nils-Erik", "initials": "NE"}, {"family": "Rubin", "given": "Kristofer", "initials": "K", "orcid": "0000-0003-2789-6276", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/60f2a0d933bf4bff95ef57efde91ac15.json"}}], "type": "journal article", "published": "2018-07-02", "journal": {"title": "Cell Commun. Signal", "issn": "1478-811X", "volume": "16", "issue": "1", "pages": "36", "issn-l": "1478-811X"}, "abstract": "Chemotherapeutic efficacy can be improved by targeting the structure and function of the extracellular matrix (ECM) in the carcinomal stroma. This can be accomplished by e.g. inhibiting TGF-\u03b21 and -\u03b23 or treating with Imatinib, which results in scarcer collagen fibril structure in xenografted human KAT-4/HT29 (KAT-4) colon adenocarcinoma.\n\nThe potential role of \u03b1V\u03b26 integrin-mediated activation of latent TGF-\u03b2 was studied in cultured KAT-4 and Capan-2 human ductal pancreatic carcinoma cells as well as in xenograft carcinoma generated by these cells. The monoclonal \u03b1V\u03b26 integrin-specific monoclonal antibody 3G9 was used to inhibit the \u03b1V\u03b26 integrin activity.\n\nBoth KAT-4 and Capan-2 cells expressed the \u03b1V\u03b26 integrin but only KAT-4 cells could utilize this integrin to activate latent TGF-\u03b2 in vitro. Only when Capan-2 cells were co-cultured with human F99 fibroblasts was the integrin activation mechanism triggered, suggesting a more complex, fibroblast-dependent, activation pathway. In nude mice, a 10-day treatment with 3G9 reduced collagen fibril thickness and interstitial fluid pressure in KAT-4 but not in the more desmoplastic Capan-2 tumors that, to achieve a similar effect, required a prolonged 3G9 treatment. In contrast, a 10-day direct inhibition of TGF-\u03b21 and -\u03b23 reduced collagen fibril thickness in both tumor models.\n\nOur data demonstrate that the \u03b1V\u03b26-directed activation of latent TGF-\u03b2 plays a pivotal role in modulating the stromal collagen network in carcinoma, but that the sensitivity to \u03b1V\u03b26 inhibition depends on the simultaneous presence of alternative paths for latent TGF-\u03b2 activation and the extent of desmoplasia.", "doi": "10.1186/s12964-018-0249-7", "pmid": "29966518", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6027735"}, {"db": "pii", "key": "10.1186/s12964-018-0249-7"}], "notes": [], "created": "2019-01-17T13:52:55.884Z", "modified": "2026-09-23T12:06:16.416Z"}, {"entity": "publication", "iuid": "d9f99d7f85024eef886798b06bd35685", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d9f99d7f85024eef886798b06bd35685.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d9f99d7f85024eef886798b06bd35685"}}, "title": "Integrin \u03b1V \u03b23 can substitute for collagen-binding \u03b21 -integrins in vivo to maintain a homeostatic interstitial fluid pressure.", "authors": [{"family": "Lid\u00e9n", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Karlsen", "given": "Tine Veronika", "initials": "TV"}, {"family": "Guss", "given": "Bengt", "initials": "B"}, {"family": "Reed", "given": "Rolf K", "initials": "RK"}, {"family": "Rubin", "given": "Kristofer", "initials": "K", "orcid": "0000-0003-2789-6276", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/60f2a0d933bf4bff95ef57efde91ac15.json"}}], "type": "journal article", "published": "2018-05-01", "journal": {"title": "Exp. Physiol.", "issn": "1469-445X", "volume": "103", "issue": "5", "pages": "629-634", "issn-l": "0958-0670"}, "abstract": "What is the central question of this study? Collagen-binding \u03b21 -integrins function physiologically in cellular control of dermal interstitial fluid pressure (PIF ) in vivo and thereby participate in control of extravascular fluid volume. During anaphylaxis, simulated by injection of compound 48/80, integrin \u03b1V \u03b23 takes over this physiological function. Here we addressed the question whether integrin \u03b1V \u03b23 can replace collagen-binding \u03b21 -integrin to maintain a long-term homeostatic PIF . What is the main finding and its importance? Mice lacking the collagen-binding integrin \u03b111 \u03b21 show a complex dermal phenotype with regard to the interstitial physiology apparent in the control of PIF . Notably dermal PIF is not lowered with compound 48/80 in these animals. Our present data imply that integrin \u03b1V \u03b23 is the likely candidate that has taken over the role of collagen-binding \u03b21 -integrins for maintaining a steady-state homeostatic PIF . A better understanding of molecular processes involved in control of PIF is instrumental for establishing novel treatment regimens for control of oedema formation in anaphylaxis and septic shock.\n\nAccumulated data indicate that cell-mediated contraction of reconstituted collagenous gels in vitro can serve as a model for cell-mediated control of interstitial fluid pressure (PIF ) in vivo. A central role for collagen-binding \u03b21 -integrins in both processes has been established. Furthermore, integrin \u03b1V \u03b23 takes over the role of collagen-binding \u03b21 -integrins in mediating contraction after perturbations of collagen-binding \u03b21 -integrins in vitro. Integrin \u03b1V \u03b23 is also instrumental for normalization of dermal PIF that has been lowered due to mast cell degranulation with compound 48/80 (C48/80) in vivo. Here we demonstrate a role of integrin \u03b1V \u03b23 in maintaining a long term homeostatic dermal PIF in mice lacking the collagen-binding integrin \u03b111 \u03b21 (\u03b111-/- mice). Measurements of PIF were performed after circulatory arrest. Furthermore, cell-mediated integrin \u03b1V \u03b23 -directed contraction of collagenous gels in vitro depends on free access to a collagen site known to bind several extracellular matrix (ECM) proteins that form substrates for \u03b1V \u03b23 -directed cell attachment, such as fibronectin and fibrin. A streptococcal collagen-binding protein, CNE, specifically binds to and blocks this site on the collagen triple helix. Here we show that whereas CNE perturbed \u03b1V \u03b23 -directed and platelet-derived growth factor BB-induced normalization of dermal PIF after C48/80, it did not affect \u03b1V \u03b23 -dependent maintenance of a homeostatic dermal PIF . These data imply that dynamic modification of the ECM structure is needed during acute patho-physiological modulations of PIF but not for long-term maintenance of a homeostatic PIF . Our data thus show that collagen-binding \u03b21 -integrins, integrin \u03b1V \u03b23 and ECM structure are potential targets for novel therapy aimed at modulating oedema formation and hypovolemic shock during anaphylaxis.", "doi": "10.1113/EP086902", "pmid": "29524327", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5947675"}], "notes": [], "created": "2018-12-05T12:41:17.597Z", "modified": "2026-09-23T13:29:36.168Z"}, {"entity": "publication", "iuid": "544f9dbaca02481283a9034f80dca602", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/544f9dbaca02481283a9034f80dca602.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/544f9dbaca02481283a9034f80dca602"}}, "title": "Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma.", "authors": [{"family": "Olsson", "given": "P Olof", "initials": "PO"}, {"family": "Kalamajski", "given": "Sebastian", "initials": "S"}, {"family": "Maccarana", "given": "Marco", "initials": "M"}, {"family": "Oldberg", "given": "\u00c5ke", "initials": "\u00c5"}, {"family": "Rubin", "given": "Kristofer", "initials": "K", "orcid": "0000-0003-2789-6276", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/60f2a0d933bf4bff95ef57efde91ac15.json"}}], "type": "journal article", "published": "2017-08-21", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "12", "issue": "8", "pages": "e0182973", "issn-l": "1932-6203"}, "abstract": "Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.", "doi": "10.1371/journal.pone.0182973", "pmid": "28827814", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5565175"}, {"db": "pii", "key": "PONE-D-16-47740"}], "notes": [], "created": "2018-12-05T12:28:28.852Z", "modified": "2026-09-23T13:04:12.413Z"}, {"entity": "publication", "iuid": "e44c9d32f6ee449d8a8fbc23ee31ece9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e44c9d32f6ee449d8a8fbc23ee31ece9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e44c9d32f6ee449d8a8fbc23ee31ece9"}}, "title": "PDGF-BB enhances collagen gel contraction through a PI3K-PLC\u03b3-PKC-cofilin pathway.", "authors": [{"family": "Reyhani", "given": "Vahid", "initials": "V"}, {"family": "Tsioumpekou", "given": "Maria", "initials": "M"}, {"family": "van Wieringen", "given": "Tijs", "initials": "T"}, {"family": "Rask", "given": "Lars", "initials": "L"}, {"family": "Lennartsson", "given": "Johan", "initials": "J"}, {"family": "Rubin", "given": "Kristofer", "initials": "K", "orcid": "0000-0003-2789-6276", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/60f2a0d933bf4bff95ef57efde91ac15.json"}}], "type": "journal article", "published": "2017-08-21", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "7", "issue": "1", "pages": "8924", "issn-l": "2045-2322"}, "abstract": "Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-stimulated platelet-derived growth factor receptor-\u03b2 (PDGF-R\u03b2). Our data show that PDGF BB-enhanced activations of phosphatidylinositol 3'-kinase (PI3K) and phospholipase C\u03b3 (PLC\u03b3) were necessary for PDGF-enhanced collagen gel contraction. Importantly, other defined signaling pathways down-stream of PDGF-R\u03b2 were, however, dispensable. The decisive roles for PI3K and PLC\u03b3 were corroborated by experiments using selective inhibitors. Furthermore, we show that de-phosphorylation and thereby activation of cofilin that is important for the turnover of actin filaments, is depended on PI3K and PLC\u03b3 down-stream of PDGF-R\u03b2. Moreover, inhibition of protein kinase C (PKC) by G\u00d66976 and bisindolylmaleimide-II abolished cofilin de-phosphorylation, as well as PDGF-enhanced contraction. In contrast, activation of the PKC protein family by 4\u03b2-phorbol 12-myristate 13-acetate (PMA) did not accelerate collagen gel contraction although it induced long-term cofilin de-phosphorylation, showing the need of a dynamic control of cofilin de-phosphorylation for PDGF-enhanced collagen gel contraction. Taken together, our data point to the involvement of a PI3K/PLC\u03b3-PKC-cofilin pathway in both PDGF-enhanced cofilin de-phosphorylation and PDGF-enhanced collagen gel contraction.", "doi": "10.1038/s41598-017-08411-1", "pmid": "28827622", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5566449"}, {"db": "pii", "key": "10.1038/s41598-017-08411-1"}], "notes": [], "created": "2018-12-05T12:09:49.082Z", "modified": "2026-09-23T10:51:41.597Z"}, {"entity": "publication", "iuid": "147f248ac2eb41498f3feb25cea5e67b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/147f248ac2eb41498f3feb25cea5e67b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/147f248ac2eb41498f3feb25cea5e67b"}}, "title": "Imatinib increases oxygen delivery in extracellular matrix-rich but not in matrix-poor experimental carcinoma.", "authors": [{"family": "Burmakin", "given": "Mikhail", "initials": "M"}, {"family": "van Wieringen", "given": "Tijs", "initials": "T"}, {"family": "Olsson", "given": "P Olof", "initials": "PO"}, {"family": "Stuhr", "given": "Linda", "initials": "L"}, {"family": "\u00c5hgren", "given": "Aive", "initials": "A"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Reed", "given": "Rolf K", "initials": "RK"}, {"family": "Rubin", "given": "Kristofer", "initials": "K", "orcid": "0000-0003-2789-6276", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/60f2a0d933bf4bff95ef57efde91ac15.json"}}, {"family": "Hellberg", "given": "Carina", "initials": "C"}], "type": "journal article", "published": "2017-02-23", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "15", "issue": "1", "pages": "47", "issn-l": "1479-5876"}, "abstract": "Imatinib causes increased turnover of stromal collagen, reduces collagen fibril diameter, enhances extracellular fluid turnover and lowers interstitial fluid pressure (IFP) in the human colonic carcinoma KAT-4/HT-29 (KAT-4) xenograft model.\n\nWe compared the effects of imatinib on oxygen levels, vascular morphology and IFP in three experimental tumor models differing in their content of a collagenous extracellular matrix.\n\nNeither the KAT4 and CT-26 colonic carcinoma models, nor B16BB melanoma expressed PDGF \u03b2-receptors in the malignant cells. KAT-4 tumors exhibited a well-developed ECM in contrast to the other two model systems. The collagen content was substantially higher in KAT-4 than in CT-26, while collagen was not detectable in B16BB tumors. The pO2 was on average 5.4, 13.9 and 19.3 mmHg in KAT-4, CT-26 and B16BB tumors, respectively. Treatment with imatinib resulted in similar pO2-levels in all three tumor models but only in KAT-4 tumors did the increase reach statistical significance. It is likely that after imatinib treatment the increase in pO2 in KAT-4 tumors is caused by increased blood flow due to reduced vascular resistance. This notion is supported by the significant reduction observed in IFP in KAT-4 tumors after imatinib treatment. Vessel area varied between 4.5 and 7% in the three tumor models and was not affected by imatinib treatment. Imatinib had no effect on the fraction of proliferating cells, whereas the fraction of apoptotic cells increased to a similar degree in all three tumor models.\n\nOur data suggest that the effects of imatinib on pO2-levels depend on a well-developed ECM and provide further support to the suggestion that imatinib acts by causing interstitial stroma cells to produce a less dense ECM, which would in turn allow for an increased blood flow. The potential of imatinib treatment to render solid tumors more accessible to conventional treatments would therefore depend on the degree of tumor desmoplasia.", "doi": "10.1186/s12967-017-1142-7", "pmid": "28231806", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5324310"}, {"db": "pii", "key": "10.1186/s12967-017-1142-7"}], "notes": [], "created": "2018-12-05T12:13:16.602Z", "modified": "2026-09-23T11:59:43.398Z"}]}