IN-VIVO MODULATION OF HUMAN TUMOR-CELL GROWTH BY NORMAL HUMAN EXTRACELLULAR-MATRIX

The extracellular matrix (ECM) is actively involved in the growth and maintenance of normal and neoplastic mammalian cells. It has been sugg ested that the growth-promoting factors sequestered within the matrix exclusively regulate the observed phenomena. We postulate, however, th at ECM components alone, when derived from normal human tissues, and d evoid of major growth factors, can modulate the growth of human tumor cells in vivo. In this submission we provide evidence that Amgel, an E CM created by us from nontumorigenic human placental tissues, can enha nce or retard human cell growth in vivo, depending upon type, when pla ced in the subcutaneous tissue of athymic mice. Further, we provide ev idence that these results differ from those obtained utilizing a tumor -derived ECM. Our findings suggest that specific tumor cell-matrix int eractions are responsible for the observed results. To the best of our knowledge, this is the first report of a normal, human tissue-derived ECM both promoting and inhibiting selected human tumor cell growth in vivo. Thus, Amgel should prove useful in elucidating the underlying m echanisms of cell-matrix interactions during the growth and progressio n of human neoplasms.