MORPHOTYPIC PLASTICITY IN-VITRO AND IN NUDE-MICE OF EPITHELIAL MOUSE MAMMARY CELLS (NMUMG) DISPLAYING AN EPITHELIOID (E) OR A FIBROBLASTIC (F) MORPHOTYPE IN CULTURE

Transition from an epithelioid (e-) to a fibroblastic (f-) morphotype marks invasiveness in clinical and experimental cancer, To understand better the factors influencing such transitions, we have subcloned and manipulated mouse mammary gland (NMuMG) cell cultures and compared th e invasive phenotype of multiple subclones in vitro and in vivo, Cell lines with an e-morphotype expressed E-cadherin homogeneously and were not invasive in vitro, Cells with an f-morphotype were E-cadherin-neg ative and became fully invasive in vitro upon expression of the vas on cogene, Invasive tumors were produced in nude mice after subcutaneous injection of e-type or f-type cells, These tumors showed cystic, gland ular and undifferentiated structures, Tumors from f-type cells were E- cadherin-negative whereas e-type tumors stained heterogeneously in imm unohistochemical preparations, Our observations demonstrate the impact of the micro-ecosystem on the invasive phenotype, with in vivo downre gulation of E-cadherin and stimulation of the e- to f-morphotype trans ition.