Cellular adhesion molecules in urologic malignancies.

Abstract

Cell adhesion molecules (CAMs) are important in cell-cell interaction and interactions between cells and components of the extracellular matrix. CAMs have been associated with invasion and metastasis in a wide variety of human malignancies, including tumors of the genitourinary tract. Cadherins are transmembrane glycoproteins that bind cells by homophilic, homotypic interactions. Loss of expression of E-cadherin has been associated with dedifferentiation, invasion, and metastasis in prostate cancer and transitional cell neoplasia of the urinary bladder. CD44, a family of transmembrane glycoproteins principally involved in cell-extracellular matrix interactions, also has been associated with invasion and metastasis in urologic malignancies. Through alternative splicing, a variety of CD44 isoforms can be expressed that can undergo extensive posttranslational modification. CD44 variants have been associated with metastasis in a variety of human malignancies, particularly in the gastrointestinal system. Although loss of expression of CD44 standard form has been associated with aggressive prostate gland and bladder cancers, no specific isoform has been associated with metastasis of these neoplasms. Integrins are transmembrane glycoproteins with wide cellular distribution that bind a variety of extracellular matrix components. Integrins have been studied extensively in prostate cancer in which altered integrin expression has been associated with malignant prostatic epithelium. Additional adhesion molecules that have been studied to a variable degree in urologic malignancies include selectins and the immunoglobulin super-family. CAMs are fundamental to diverse biologic processes and appear capable of regulating intracellular signaling events that appear to have significant importance in human malignancy, including cancers of the urogenital tract.