Distribution of VLA integrins in solid tumors. Emergence of tumor-type-related expression. Patterns in carcinomas and sarcomas.
Integrins form a family of membrane-spanning cell-surface proteins that promote cell-cell or cell-matrix adhesion and integrate the pericellular matrix to the cytoskeleton. Integrins are believed to be involved in the differentiation of tissues during development. They are involved in the relationship of tumor cells to the matrix and may on the other hand reflect the differentiation status of cells. In this study, we evaluated immunohistochemically the distribution of VLA integrins (alpha 1 to alpha 6 chains of beta 1 integrins) in a representative selection of normal tissues and 110 solid tumors. In simple epithelia, VLA2 and VLA3 were usually uniformly present in epithelial cells, whereas in ductal and stratified epithelia they were seen predominantly in the basal/myoepithelial cells. VLA6 was seen in the basal aspect of epithelia in a polar manner. In carcinomas, VLA2 and VLA3 were variably expressed, showing either basal distribution in cellular islands or generalized widespread distribution or rarely being absent. VLA2 and VLA3 were also seen in epithelial components of epitheliomesenchymal tumors. VLA1 and VLA5 were widely distributed in benign and malignant mesenchymal tumors and in the desmoplastic stroma of carcinomas. They were usually not seen in epithelia, except that VLA1 was present in myoepithelia of the breast and VLA5 occasionally in poorly differentiated carcinoma cells. Mesenchymal cell/tumor types had characteristic patterns of VLA integrins; for example, smooth muscle and its benign tumors showed VLA1, 3, and 5, whereas schwannomas showed VLA1, 2, 3 and 6. Endothelial cells and angiosarcomas showed multiple VLA-types: VLA1, 2, 3, 5, and 6 in a similar manner. In malignant schwannomas and leiomyosarcomas, moderate to extensive reduction of expression of VLA2, 3, and 6 and of VLA3 and 5, respectively, occurred. The results show that VLA (beta 1) integrins show characteristic cell lineage-dependent distribution patterns in solid tumors and are a potentially useful tool in tumor typing.
Miettinen
M
M
Department of Pathology and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5098.
Castello
R
R
Wayner
E
E
Schwarting
R
R
D002277:Carcinoma / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009369:Neoplasms / Q000145:classification* / Q000378:metabolism*; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D012016:Reference Values; D012509:Sarcoma / Q000378:metabolism*; D013194:Staining and Labeling; D014018:Tissue Distribution
D016029:Receptors, Very Late Antigen