DIFFERENTIAL EXPRESSION OF BETA-1 INTEGRINS IN NONNEOPLASTIC SMOOTH AND STRIATED-MUSCLE CELLS AND IN TUMORS DERIVED FROM THESE CELLS

Integrins are a superfamily of transmembrane alpha beta heterodimers t hat play an important role in cell-matrix and cell-cell interactions b y acting as receptors for extracellular matrix proteins and for cell a dhesion molecules. Using monoclonal antibodies against beta 1, alpha 1 to alpha 6, and alpha v subunits, the in situ distribution pattern of beta 1 integrins was examined immunohistochemically in nonneoplastic smooth and striated muscle cells and in their tumors. Nonneoplastic sm ooth muscle cells were beta 1(+), alpha 1(+), alpha 3(+), alpha v(+) a nd, in diverse localizations, also alpha 5(+) or even alpha 6(+). Tbe expression of the beta 1 chain was conserved in all leiomyomas and lei omyosarcomas. The distribution pattern of the alpha subunits by contra st underwent several changes during malignant transformation of smooth muscle cells. These alterations consisted in a neoexpression of alpha 2, alpha 4, and alpha 6 as well as in an abnormal abrogation of alpha 1 and alpha 3 in some leiomyosarcomas. Except for the absence of alph a 5 in the majority of epithelioid leiomyosarcomas, expression of the alpha 5 and m,subunits was mainly conserved. In addition, tumors with epithelioid differentiation differed from typical cases by the absence of alpha 1 and the simultaneous presence of alpha 4. Adult striated m uscle cells were beta 1(+) but alpha 1(-) to alpha 6(-) and alpha v(-) , whereas fetal striated muscle cells were not only beta 1(+) but also alpha 3(+/-), alpha 4(+/-), alpha 5(+) and alpha 6(+). In all rhabdom yosarcomas the expression of beta 1 was retained. Furthermore, the maj ority of cases showed the expression of one or more alpha subunits mos t of which, ie, alpha 4, alpha 5, and alpha 6, were also found in feta l striated muscle cells. In conclusion, beta 1 integrins exhibited a d ifferential expression pattern along the two lines of myogenic differe ntiation. This integrin profile underwent characteristic changes durin g malignant transformation Nevertheless, the compiled distribution pat terns of the alpha 1, alpha 3, and alpha v subunits allowed in most in stances the discrimination between tumors of smooth (alpha 1(+) / alph a 3(+) / alpha v(+)) and striated muscle (alpha 1(-) / alpha 3(-) / al pha v(-)) differentiation.