Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils

doi:10.1083/jcb.115.5.1427

This Article

	Full Text (PDF, 1570K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Klein, C. E.
	Articles by Weber, L.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Klein, C. E.
	Articles by Weber, L.


Social Bookmarking

	What's this?

ARTICLES

Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils

CE Klein, D Dressel, T Steinmayer, C Mauch, B Eckes, T Krieg, RB Bankert and L Weber
Department of Dermatology, University of Ulm, Germany.

The ability of cultured human fibroblasts to reorganize and contract three dimensional collagen I gels is regarded as an in vitro model for the reorganization of connective tissue during wound healing. We investigated whether adhesion receptors of the integrin family are involved. It was found that synthesis and transcription of the alpha 2 beta 1 integrin (but not of alpha 1 beta 1 or alpha 3 beta 1) is selectively upregulated when fibroblasts are seeded into type I collagen gels. Time course experiments revealed that high synthetic levels of alpha 2 beta 1 parallel the gel contraction process and return to "baseline" levels after the contraction has subsided. Furthermore, function-blocking mAbs directed to the alpha 2 and beta 1 chain of integrins inhibited gel contraction. Remodelling of connective tissue can be important for tumor cells during invasion and formation of metastases. Therefore, we tested human melanoma cell lines for this function. Five out of nine melanoma lines contracted collagen gels in vitro. Among these, two highly aggressive melanoma cell lines (MV3 and BLM) most efficiently contracted gels almost reaching the rate of normal adult fibroblasts. In these cells, synthesis of alpha 2 beta 1 was also significantly upregulated when seeded into collagen I gels. Moreover, function blocking anti-alpha 2 in conjunction with anti-beta 1 chain mAbs completely inhibited gel contraction for several days. Other melanoma cells (530) with lower metastatic potential which were not able to contract gels, showed no induction of alpha 2 beta 1 synthesis in gel culture. Our results suggest an important role of integrin alpha 2 beta 1 in the contraction of collagen I by normal diploid fibroblasts during wound healing and in the reorganization of collagen matrices by highly aggressive human melanoma cells.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Svendsen, O.S., Barczyk, M.M., Popova, S.N., Liden, A, Gullberg, D., Wiig, H. (2009). The {alpha}11{beta}1 Integrin Has a Mechanistic Role in Control of Interstitial Fluid Pressure and Edema Formation in Inflammation. Arterioscler. Thromb. Vasc. Bio. 29: 1864-1870 [Abstract] [Full Text]
Schissel, S. L., Dunsmore, S. E., Liu, X., Shine, R. W., Perrella, M. A., Layne, M. D. (2009). Aortic Carboxypeptidase-Like Protein Is Expressed in Fibrotic Human Lung and its Absence Protects against Bleomycin-Induced Lung Fibrosis. Am. J. Pathol. 174: 818-828 [Abstract] [Full Text]
Kamio, K., Liu, X., Sugiura, H., Togo, S., Kobayashi, T., Kawasaki, S., Wang, X., Mao, L., Ahn, Y., Hogaboam, C., Toews, M. L., Rennard, S. I. (2007). Prostacyclin Analogs Inhibit Fibroblast Contraction of Collagen Gels through the cAMP-PKA Pathway. Am. J. Respir. Cell Mol. Bio. 37: 113-120 [Abstract] [Full Text]
Tura, A., Grisanti, S., Petermeier, K., Henke-Fahle, S. (2007). The Rho-Kinase Inhibitor H-1152P Suppresses the Wound-Healing Activities of Human Tenon's Capsule Fibroblasts In Vitro. IOVS 48: 2152-2161 [Abstract] [Full Text]
Hozumi, K., Suzuki, N., Nielsen, P. K., Nomizu, M., Yamada, Y. (2006). Laminin {alpha}1 Chain LG4 Module Promotes Cell Attachment through Syndecans and Cell Spreading through Integrin {alpha}2beta1. J. Biol. Chem. 281: 32929-32940 [Abstract] [Full Text]
Zhang, Z.-G., Bothe, I., Hirche, F., Zweers, M., Gullberg, D., Pfitzer, G., Krieg, T., Eckes, B., Aumailley, M. (2006). Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of {alpha}2{beta}1 integrin.. J. Cell Sci. 119: 1886-1895 [Abstract] [Full Text]
Franco, C., Ho, B., Mulholland, D., Hou, G., Islam, M., Donaldson, K., Bendeck, M. P. (2006). Doxycycline Alters Vascular Smooth Muscle Cell Adhesion, Migration, and Reorganization of Fibrillar Collagen Matrices. Am. J. Pathol. 168: 1697-1709 [Abstract] [Full Text]
Meierjohann, S., Wende, E., Kraiss, A., Wellbrock, C., Schartl, M. (2006). The oncogenic epidermal growth factor receptor variant xiphophorus melanoma receptor kinase induces motility in melanocytes by modulation of focal adhesions.. Cancer Res. 66: 3145-3152 [Abstract] [Full Text]
Jiang, H., Grinnell, F. (2005). Cell-Matrix Entanglement and Mechanical Anchorage of Fibroblasts in Three-dimensional Collagen Matrices. Mol. Biol. Cell 16: 5070-5076 [Abstract] [Full Text]
Lunter, P. C., van Kilsdonk, J. W.J., van Beek, H., Cornelissen, I. M.H.A., Bergers, M., Willems, P. H.G.M., van Muijen, G. N.P., Swart, G. W.M. (2005). Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166/MEMD), a Novel Actor in Invasive Growth, Controls Matrix Metalloproteinase Activity. Cancer Res. 65: 8801-8808 [Abstract] [Full Text]
Kaido, T., Yebra, M., Cirulli, V., Montgomery, A. M. (2004). Regulation of Human {beta}-Cell Adhesion, Motility, and Insulin Secretion by Collagen IV and Its Receptor {alpha}1{beta}1. J. Biol. Chem. 279: 53762-53769 [Abstract] [Full Text]
Baronas-Lowell, D., Lauer-Fields, J. L., Borgia, J. A., Sferrazza, G. F., Al-Ghoul, M., Minond, D., Fields, G. B. (2004). Differential Modulation of Human Melanoma Cell Metalloproteinase Expression by {alpha}2{beta}1 Integrin and CD44 Triple-helical Ligands Derived from Type IV Collagen. J. Biol. Chem. 279: 43503-43513 [Abstract] [Full Text]
Jokinen, J., Dadu, E., Nykvist, P., Kapyla, J., White, D. J., Ivaska, J., Vehvilainen, P., Reunanen, H., Larjava, H., Hakkinen, L., Heino, J. (2004). Integrin-mediated Cell Adhesion to Type I Collagen Fibrils. J. Biol. Chem. 279: 31956-31963 [Abstract] [Full Text]
Breitkreutz, D., Mirancea, N., Schmidt, C., Beck, R., Werner, U., Stark, H.-J., Gerl, M., Fusenig, N. E. (2004). Inhibition of basement membrane formation by a nidogen-binding laminin {gamma}1-chain fragment in human skin-organotypic cocultures. J. Cell Sci. 117: 2611-2622 [Abstract] [Full Text]
Stuhr, L. E. B., Reith, A., Lepsoe, S., Myklebust, R., Wiig, H., Reed, R. K. (2003). Fluid pressure in human dermal fibroblast aggregates measured with micropipettes. Am. J. Physiol. Cell Physiol. 285: C1101-C1108 [Abstract] [Full Text]
Li, S., Van Den Diepstraten, C., D'Souza, S. J., Chan, B. M. C., Pickering, J. G. (2003). Vascular Smooth Muscle Cells Orchestrate the Assembly of Type I Collagen via {alpha}2{beta}1 Integrin, RhoA, and Fibronectin Polymerization. Am. J. Pathol. 163: 1045-1056 [Abstract] [Full Text]
Guidry, C., Bradley, K. M., King, J. L. (2003). Tractional Force Generation by Human Muller Cells: Growth Factor Responsiveness and Integrin Receptor Involvement. IOVS 44: 1355-1363 [Abstract] [Full Text]
Holleran, B. J., Barbar, E., Payet, M. D., Dupuis, G. (2003). Differential recruitment of {alpha}2{beta}1 and {alpha}4{beta}1 integrins to lipid rafts in Jurkat T lymphocytes exposed to collagen type IV and fibronectin. J. Leukoc. Biol. 73: 243-252 [Abstract] [Full Text]
Tamariz, E., Grinnell, F. (2002). Modulation of Fibroblast Morphology and Adhesion during Collagen Matrix Remodeling. Mol. Biol. Cell 13: 3915-3929 [Abstract] [Full Text]
Zigrino, P., Kamiguti, A. S., Eble, J., Drescher, C., Nischt, R., Fox, J. W., Mauch, C. (2002). The Reprolysin Jararhagin, a Snake Venom Metalloproteinase, Functions as a Fibrillar Collagen Agonist Involved in Fibroblast Cell Adhesion and Signaling. J. Biol. Chem. 277: 40528-40535 [Abstract] [Full Text]
Prasad, N., Topping, R. S., Decker, S. J. (2002). Src family tyrosine kinases regulate adhesion-dependent tyrosine phosphorylation of 5'-inositol phosphatase SHIP2 during cell attachment and spreading on collagen I. J. Cell Sci. 115: 3807-3815 [Abstract] [Full Text]
Rabinovitz, I., Gipson, I. K., Mercurio, A. M. (2001). Traction Forces Mediated by alpha 6beta 4 Integrin: Implications for Basement Membrane Organization and Tumor Invasion. Mol. Biol. Cell 12: 4030-4043 [Abstract] [Full Text]
Rocnik, E., Saward, L., Pickering, J. G. (2001). HSP47 Expression by Smooth Muscle Cells Is Increased During Arterial Development and Lesion Formation and Is Inhibited by Fibrillar Collagen. Arterioscler. Thromb. Vasc. Bio. 21: 40-46 [Abstract] [Full Text]
Kelynack, K. J., Hewitson, T. D., Nicholls, K. M., Darby, I. A., Becker, G. J. (2000). Human renal fibroblast contraction of collagen I lattices is an integrin-mediated process. Nephrol Dial Transplant 15: 1766-1772 [Abstract] [Full Text]
Hocking, D. C., Sottile, J., Langenbach, K. J. (2000). Stimulation of Integrin-mediated Cell Contractility by Fibronectin Polymerization. J. Biol. Chem. 275: 10673-10682 [Abstract] [Full Text]
Nykvist, P., Tu, H., Ivaska, J., Kapyla, J., Pihlajaniemi, T., Heino, J. (2000). Distinct Recognition of Collagen Subtypes by alpha 1beta 1 and alpha 2beta 1 Integrins. alpha 1beta 1 MEDIATES CELL ADHESION TO TYPE XIII COLLAGEN. J. Biol. Chem. 275: 8255-8261 [Abstract] [Full Text]
Cooke, M., Sakai, T, Mosher, D. (2000). Contraction of collagen matrices mediated by alpha2beta1A and alpha(v)beta3 integrins. J. Cell Sci. 113: 2375-2383 [Abstract]
Aumailley, M, Pesch, M, Tunggal, L, Gaill, F, Fassler, R (2000). Altered synthesis of laminin 1 and absence of basement membrane component deposition in (beta)1 integrin-deficient embryoid bodies. J. Cell Sci. 113: 259-268 [Abstract]
Ivaska, J., Reunanen, H., Westermarck, J., Koivisto, L., Kahari, V.-M., Heino, J. (1999). Integrin {alpha}2{beta}1 Mediates Isoform-Specific Activation of p38 and Upregulation of Collagen Gene Transcription by a Mechanism Involving the {alpha}2 Cytoplasmic Tail. JCB 147: 401-416 [Abstract] [Full Text]
Maaser, K., Wolf, K., Klein, C. E., Niggemann, B., Zänker, K. S., Bröcker, E.-B., Friedl, P. (1999). Functional Hierarchy of Simultaneously Expressed Adhesion Receptors: Integrin alpha 2beta 1 but Not CD44 Mediates MV3 Melanoma Cell Migration and Matrix Reorganization within Three-dimensional Hyaluronan-containing Collagen Matrices. Mol. Biol. Cell 10: 3067-3079 [Abstract] [Full Text]
Ryu, J. S., Majeska, R. J., Ma, Y., LaChapelle, L., Guller, S. (1999). Steroid Regulation of Human Placental Integrins: Suppression of {alpha}2 Integrin Expression in Cytotrophoblasts by Glucocorticoids. Endocrinology 140: 3904-3908 [Abstract] [Full Text]
Maniotis, A. J., Folberg, R., Hess, A., Seftor, E. A., Gardner, L. M.G., Pe'er, J., Trent, J. M., Meltzer, P. S., Hendrix, M. J. C. (1999). Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry. Am. J. Pathol. 155: 739-752 [Abstract] [Full Text]
KAGAMI, S., KONDO, S., LÖSTER, K., REUTTER, W., KUHARA, T., YASUTOMO, K., KURODA, Y. (1999). {alpha}1{beta}1 Integrin-Mediated Collagen Matrix Remodeling by Rat Mesangial Cells Is Differentially Regulated by Transforming Growth Factor-{beta} and Platelet-Derived Growth Factor-BB. J. Am. Soc. Nephrol. 10: 779-789 [Abstract] [Full Text]
Arora, P. D., Narani, N., McCulloch, C. A. G. (1999). The Compliance of Collagen Gels Regulates Transforming Growth Factor-� Induction of {alpha}-Smooth Muscle Actin in Fibroblasts. Am. J. Pathol. 154: 871-882 [Abstract] [Full Text]
Grinnell, F., Ho, C.-H., Lin, Y.-C., Skuta, G. (1999). Differences in the Regulation of Fibroblast Contraction of Floating Versus Stressed Collagen Matrices. J. Biol. Chem. 274: 918-923 [Abstract] [Full Text]
Gardner, H, Broberg, A, Pozzi, A, Laato, M, Heino, J (1999). Absence of integrin alpha1beta1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis. J. Cell Sci. 112: 263-272 [Abstract]
Scherberich, A., Moog, S., Haan-Archipoff, G., Azorsa, D. O., Lanza, F., Beretz, A. (1998). Tetraspanin CD9 Is Associated With Very Late�Acting Integrins in Human Vascular Smooth Muscle Cells and Modulates Collagen Matrix Reorganization. Arterioscler. Thromb. Vasc. Bio. 18: 1691-1697 [Abstract] [Full Text]
Carnevali, S., Nakamura, Y., Mio, T., Liu, X., Takigawa, K., Romberger, D. J., Spurzem, J. R., Rennard, S. I. (1998). Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction. Am. J. Physiol. Lung Cell. Mol. Physiol. 274: L591-L598 [Abstract] [Full Text]
Xu, J., Zutter, M. M., Santoro, S. A., Clark, R. A.F. (1998). A Three-dimensional Collagen Lattice Activates NF-{kappa}B in Human Fibroblasts: Role in Integrin {alpha}2 Gene Expression and Tissue Remodeling. JCB 140: 709-719 [Abstract] [Full Text]
Berg, A., Ekwall, A.-K. H., Rubin, K., Stjernschantz, J., Reed, R. K. (1998). Effect of PGE1, PGI2, and PGF2alpha analogs on collagen gel compaction in vitro and interstitial pressure in vivo. Am. J. Physiol. Heart Circ. Physiol. 274: H663-H671 [Abstract] [Full Text]
Eckes, B, Dogic, D, Colucci-Guyon, E, Wang, N, Maniotis, A, Ingber, D, Merckling, A, Langa, F, Aumailley, M, Delouvee, A, Koteliansky, V, Babinet, C, Krieg, T (1998). Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts. J. Cell Sci. 111: 1897-1907 [Abstract]
Racine-Samson, L., Rockey, D. C., Bissell, D. M. (1997). The Role of alpha 1beta 1 Integrin in Wound Contraction. A QUANTITATIVE ANALYSIS OF LIVER MYOFIBROBLASTS IN VIVO AND IN PRIMARY CULTURE. J. Biol. Chem. 272: 30911-30917 [Abstract] [Full Text]
Ho, W.-c., Heinemann, C., Hangan, D., Uniyal, S., Morris, V. L., Chan, B. M.C. (1997). Modulation of In Vivo Migratory Function of alpha 2beta 1 Integrin in Mouse Liver. Mol. Biol. Cell 8: 1863-1875 [Abstract] [Full Text]
Camper, L., Heinegard, D., Lundgren-Akerlund, E. (1997). Integrin {alpha}2{beta}1 Is a Receptor for the Cartilage Matrix Protein Chondroadherin. JCB 138: 1159-1167 [Abstract] [Full Text]
Xu, J., Clark, R. A.F. (1997). A Three-dimensional Collagen Lattice Induces Protein Kinase C-{zeta} Activity: Role in {alpha}2 Integrin and Collagenase mRNA Expression. JCB 136: 473-483 [Abstract] [Full Text]
Greiling, D, Clark, R. (1997). Fibronectin provides a conduit for fibroblast transmigration from collagenous stroma into fibrin clot provisional matrix. J. Cell Sci. 110: 861-870 [Abstract]
Deryugina, E. I., Bourdon, M. A. (1996). Tenascin mediates human glioma cell migration and modulates cell migration on fibronectin. J. Cell Sci. 109: 643-652 [Abstract]
Echtermeyer, F., Sch�ber, S., P�schl, E., von der Mark, H., von der Mark, K. (1996). Specific Induction of Cell Motility on Laminin by alpha7 Integrin. J. Biol. Chem. 271: 2071-2075 [Abstract] [Full Text]
Schaefer, T, Roux, M, Stuhlsatz, H., Herken, R, Coulomb, B, Krieg, T, Smola, H (1996). Glycosaminoglycans modulate cell-matrix interactions of human fibroblasts and endothelial cells in vitro. J. Cell Sci. 109: 479-488 [Abstract]
Hardwick, C., Morris, R., Witherspoon, D., White, M., Feist, R., McFarland, R., Guidry, C. (1995). Pathologic Human Vitreous Promotes Contraction by Fibroblasts: Implications for Proliferative Vitreoretinopathy. Arch Ophthalmol 113: 1545-1553 [Abstract]
Hoshiga, M., Alpers, C. E., Smith, L. L., Giachelli, C. M., Schwartz, S. M. (1995). {alpha}v�3 Integrin Expression in Normal and Atherosclerotic Artery. Circ. Res. 77: 1129-1135 [Abstract] [Full Text]
Delcommenne, M., Streuli, C. H. (1995). Control of Integrin Expression by Extracellular Matrix. J. Biol. Chem. 270: 26794-26801 [Abstract] [Full Text]
Riikonen, T., Westermarck, J., Koivisto, L., Broberg, A., K�h�ri, V.-M., Heino, J. (1995). Integrin [IMAGE]2[IMAGE]1 Is a Positive Regulator of Collagenase (MMP-1) and Collagen [IMAGE]1(I) Gene Expression. J. Biol. Chem. 270: 13548-13552 [Abstract] [Full Text]
Lee, R. T., Berditchevski, F., Cheng, G. C., Hemler, M. E. (1995). Integrin-Mediated Collagen Matrix Reorganization by Cultured Human Vascular Smooth Muscle Cells. Circ. Res. 76: 209-214 [Abstract] [Full Text]
Katagiri, Y., Hiroyama, T., Akamatsu, N., Suzuki, H., Yamazaki, H., Tanoue, K. (1995). Involvement of alpha(v)beta(3) Integrin in Mediating Fibrin Gel Retraction. J. Biol. Chem. 270: 1785-1790 [Abstract] [Full Text]
Riikonen, T., Koivisto, L., Vihinen, P., Heino, J. (1995). Transforming Growth Factor-beta Regulates Collagen Gel Contraction by Increasing alpha2beta1 Integrin Expression in Osteogenic Cells. J. Biol. Chem. 270: 376-382 [Abstract] [Full Text]
Clark, R., Nielsen, L., Welch, M., McPherson, J. (1995). Collagen matrices attenuate the collagen-synthetic response of cultured fibroblasts to TGF-beta. J. Cell Sci. 108: 1251-1261 [Abstract]
Keely, P., Fong, A., Zutter, M., Santoro, S. (1995). Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha 2 integrin mRNA in mammary cells. J. Cell Sci. 108: 595-607 [Abstract]
Lee, T., Lin, Y., Mochitate, K, Grinnell, F (1993). Stress-relaxation of fibroblasts in collagen matrices triggers ectocytosis of plasma membrane vesicles containing actin, annexins II and VI, and beta 1 integrin receptors. J. Cell Sci. 105: 167-177 [Abstract]
Zambruno, G, Marchisio, P., Melchiori, A, Bondanza, S, Cancedda, R, De Luca, M (1993). Expression of integrin receptors and their role in adhesion, spreading and migration of normal human melanocytes. J. Cell Sci. 105: 179-190 [Abstract]
Kessler, D., Dethlefsen, S., Haase, I., Plomann, M., Hirche, F., Krieg, T., Eckes, B. (2001). Fibroblasts in Mechanically Stressed Collagen Lattices Assume a "Synthetic" Phenotype. J. Biol. Chem. 276: 36575-36585 [Abstract] [Full Text]
Fringer, J., Grinnell, F. (2001). Fibroblast Quiescence in Floating or Released Collagen Matrices. CONTRIBUTION OF THE ERK SIGNALING PATHWAY AND ACTIN CYTOSKELETAL ORGANIZATION. J. Biol. Chem. 276: 31047-31052 [Abstract] [Full Text]