Cancer and Metastasis Reviews 10: 4%59, 1991. © 1991Kluwer Academic Publishers. Printed in the Netherlands.
Integrin expression in malignant melanoma Randall H. Kramer 1 3, Mai Vu 1, Yao-Fen Cheng I and Daniel M. Ramos 1 Departments of ~Stomatology and 2Anatomy and the 3Cardiovascular Research Institute, University of California, San Francisco, CA, USA
Key words: melanoma, metastasis, integrins, extracellular matrix, laminin
Abstract
Invasion of melanoma cells into the underlying interstitial stromal matrix is the initial step for subsequent local and distant metastasis. The invading tumor cell must interact with the extracellular matrix during the early stages of invasion and later during penetration of lymphatic and blood vessels. This interaction with different types of extracellular matrix predicts that the invasive cell must possess surface adhesion receptors with diverse ligand specificities, including the capacity to bind different types of collagens and adhesive glycoproteins. Metastatic melanoma cells do in fact express multiple adhesion receptors, including several of the receptors from the integrin family of heterodimers. The integrin receptors can be either extremely specific for a single iigand or capable of binding multiple ligands. It is likely that the tumor cell's repertoire of adhesion receptors may influence not only its adhesive properties but its metastatic characteristics as well. There is evidence that normal melanocytes have an integrin profile distinct from that of melanoma cells. In particular, melanocytes adhere poorly to laminin while metastatic melanoma cells bind well to this ligand. This difference in adhesion between the two cell types appears to reflect the fact that melanoma cells express a melanoma-specific integrin (c~7~) that binds laminin and is not detectable in normal melanocytes. The presence of increased laminin receptors and enhanced laminin binding in melanoma cells may contribute to the malignant phenotype.
Role of adhesion receptors in invasion and metastasis
Malignant melanoma is a highly invasive and metastatic tumor whose incidence in recent years has been on the increase. The clinical outcome for melanoma relates directly to the thickness of the primary tumor and the depth to which the melanoma cells have penetrated the underlying dermis and subcutaneous tissues (Herlyn, 1990; Liotta, 1987). Eventually, these invading cells gain access to lymphatic and blood vessels, giving them the opportunity to form distant metastases. Once dissemination has occurred, the prognosis is extremely poor. The ability of tumor cells to invade through the dermal-epidermal basement membrane and
then penetrate the interstitial extracellular matrix is dependent on their capacity to adhere to, interact with, and migrate through these matrices. These interactions require that the invasive cell possess an appropriate set of adhesion receptors. Initially, melanoma cells in the early primary tumor must penetrate the adjacent epidermal basement membrane and enter the interstitial stroma of the dermis. This process clearly involves specific interactions between tumor-cell-surface adhesion receptors and multiple adhesive components of the extracellular matrix. Later, during hematogenous colonization, tumor cell emboli that have penetrated the microvascular endothelium must be able to adhere rapidly and firmly to the exposed basement membrane. It is reasonable, then, that meta-
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Integrin expression in malignant melanoma Randall H. Kramer 1 3, Mai Vu 1, Yao-Fen Cheng I and Daniel M. Ramos 1 Departments of ~Stomatology and 2Anatomy and the 3Cardiovascular Research Institute, University of California, San Francisco, CA, USA
Key words: melanoma, metastasis, integrins, extracellular matrix, laminin
Abstract
Invasion of melanoma cells into the underlying interstitial stromal matrix is the initial step for subsequent local and distant metastasis. The invading tumor cell must interact with the extracellular matrix during the early stages of invasion and later during penetration of lymphatic and blood vessels. This interaction with different types of extracellular matrix predicts that the invasive cell must possess surface adhesion receptors with diverse ligand specificities, including the capacity to bind different types of collagens and adhesive glycoproteins. Metastatic melanoma cells do in fact express multiple adhesion receptors, including several of the receptors from the integrin family of heterodimers. The integrin receptors can be either extremely specific for a single iigand or capable of binding multiple ligands. It is likely that the tumor cell's repertoire of adhesion receptors may influence not only its adhesive properties but its metastatic characteristics as well. There is evidence that normal melanocytes have an integrin profile distinct from that of melanoma cells. In particular, melanocytes adhere poorly to laminin while metastatic melanoma cells bind well to this ligand. This difference in adhesion between the two cell types appears to reflect the fact that melanoma cells express a melanoma-specific integrin (c~7~) that binds laminin and is not detectable in normal melanocytes. The presence of increased laminin receptors and enhanced laminin binding in melanoma cells may contribute to the malignant phenotype.
Role of adhesion receptors in invasion and metastasis
Malignant melanoma is a highly invasive and metastatic tumor whose incidence in recent years has been on the increase. The clinical outcome for melanoma relates directly to the thickness of the primary tumor and the depth to which the melanoma cells have penetrated the underlying dermis and subcutaneous tissues (Herlyn, 1990; Liotta, 1987). Eventually, these invading cells gain access to lymphatic and blood vessels, giving them the opportunity to form distant metastases. Once dissemination has occurred, the prognosis is extremely poor. The ability of tumor cells to invade through the dermal-epidermal basement membrane and
then penetrate the interstitial extracellular matrix is dependent on their capacity to adhere to, interact with, and migrate through these matrices. These interactions require that the invasive cell possess an appropriate set of adhesion receptors. Initially, melanoma cells in the early primary tumor must penetrate the adjacent epidermal basement membrane and enter the interstitial stroma of the dermis. This process clearly involves specific interactions between tumor-cell-surface adhesion receptors and multiple adhesive components of the extracellular matrix. Later, during hematogenous colonization, tumor cell emboli that have penetrated the microvascular endothelium must be able to adhere rapidly and firmly to the exposed basement membrane. It is reasonable, then, that meta-
50 o~1 (z 2 o~3
154
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