Function and Developmental Regulation of Matrix Receptors

Yamada, K.

Abstract

Integrins and other receptors for extracellular matrix proteins such as fibronectin, collagen, and laminin are thought to play important roles in embryonic development and metastasis. Monoclonal antibodies against specific integrins and recombinant DNA approaches are being applied to understand their mechanisms of function, as well as the developmental or potential medical sequelae of inhibiting such receptors. Inhibition of certain beta1 integrin receptors blocked migration of a variety of cell types in vitro and disrupted normal embryonic development. Migration of human keratinocytes and several tumor lines on fibronectin depended on normal function of the mature form of the integrin alpah5 beta1, whereas migration of various cells in collagen was dependent on alpha2 beta1. Rates of cell migration depended on the avidity of receptor-substrate interactions. The essential function of such receptors in tumor cell migration and invasion was demonstrated in vitro and is being tested in vivo. A non-integrin 47 kD protein that also binds to collagen and is decreased in malignant cells was sequenced at the cDNA level and shown to be a member of the serpin family. Regulation of the localization and functional association of matrix receptors with the cytoskeleton is currently being explored using novel intermolecular chimeras.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Dental & Craniofacial Research (NIDCR)
• Type: Intramural Research (Z01)
• Project #: 1Z01DE000524-01
• Application #: 3854256
• Support Year: 1
• Fiscal Year: 1991

Institution

• Name: National Institute of Dental & Craniofacial Research
• Country: United States

Publications

Petrie, Ryan J; Yamada, Kenneth M (2012) At the leading edge of three-dimensional cell migration. J Cell Sci 125:5917-26

Doyle, Andrew D; Wang, Francis W; Matsumoto, Kazue et al. (2009) One-dimensional topography underlies three-dimensional fibrillar cell migration. J Cell Biol 184:481-90

Sameni, Mansoureh; Dosescu, Julie; Yamada, Kenneth M et al. (2008) Functional live-cell imaging demonstrates that beta1-integrin promotes type IV collagen degradation by breast and prostate cancer cells. Mol Imaging 7:199-213

Galbraith, Catherine G; Yamada, Kenneth M; Galbraith, James A (2007) Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science 315:992-5

Berrier, Allison L; Yamada, Kenneth M (2007) Cell-matrix adhesion. J Cell Physiol 213:565-73

Even-Ram, Sharona; Doyle, Andrew D; Conti, Mary Anne et al. (2007) Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol 9:299-309

Green, J Angelo; Yamada, Kenneth M (2007) Three-dimensional microenvironments modulate fibroblast signaling responses. Adv Drug Deliv Rev 59:1293-8

Stepp, Mary Ann; Liu, Yueyuan; Pal-Ghosh, Sonali et al. (2007) Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1. J Cell Sci 120:2851-63

Mattiussi, Stefania; Matsumoto, Kazue; Illi, Barbara et al. (2006) Papilloma protein E6 abrogates shear stress-dependent survival in human endothelial cells: evidence for specialized functions of paxillin. Cardiovasc Res 70:578-88

Artym, Vira V; Zhang, Ying; Seillier-Moiseiwitsch, Francoise et al. (2006) Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Cancer Res 66:3034-43