The Effects of Calcium, Epidermal Growth Factor and Retinoic Acid on A9/ α6 β4 Integrin Expression of Normal and Malignant Keratoinocytes In Vitro
Reinke, Timothy S.
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Monoclonal antibody UM-A9 defines the α6 4β intergrin associated with aggressive human squamous carcinomas (Van Waes et al.) 1991) . A9 antigen was found to be selectively expressed on only the basal surface of normal keratinocytes in culture while some squamous carcinoma cell lines express more A9/ α6 4β antigen. Where both primary and metastatic tumor cells lines were established from the same patient, the metastatic tumors expressed more A9/ α6 4β antigen than the primary, with expression on the basal as well apical surfaces (Carey et al. 1990). These observations suggest an association of A9/ α6 4β expression and biological behavior of malignancy (Kimmel and Carey 1986) . High expression of A9 antigen on patient's tumors grown in culture is associated with early relapse and death. As a biological marker of tumor progression, A9 antigen has predictive value in clinical behavior of tumors (Wolf et al, 1990}. Whether A9 expression functions directly in clinical progression of squamous cancers is not yet known. We studied morphology and A9 antigen expression on normal and malignant keratinocytes in vitro challenged by Epidermal Growth Factor (EGF) , Calcium (Ca++) and Retinoic acid (RA), a growth promotional factor, an inducer of differentiation, and an inhibitor of differentiation respectively. We were interested in the effects of these chemicals on α6 4β expression, in particular how normal and malignant keratinocytes differ in expression of A9/ α6 4β when grown in different defined medias. Normal and malignant keratinocytes grown in the presence of calcium showed altered morphology. For cells grown in EGF, an increase in expression was seen. Down regulation or polarization of the A9/ α6 4β integrin for normal keratinocytes grown in media containing EGF plus Ca++ was seen, whereas malignant cells maintained basal as well as apical expression of α6 4β integrin. Normal cells grown in media containing RA without calcium down regulated expression whereas the same cells grown in RA plus calcium showed up regulation of A9/ α6 4β integrin. A9/ α6 4β antigen expression on malignant keratinocytes was unchanged through out the experiment.