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 suggested that the growth-promoting factors sequestered within the matrix exclusively regulate the observed phenomena. We postulate, however, that ECM components alone, when derived from normal human tissues, and devoid of major growth factors, can modulate the growth of human tumor cells in vivo. In this submission we provide evidence that Amgel, an ECM created by us from nontumorigenic human placental tissues, can enhance or retard human cell growth in vivo, depending upon type, when placed in the subcutaneous tissue of athymic mice. Further, we provide evidence that these results differ from those obtained utilizing a tumor-derived ECM. Our findings suggest that specific tumor cell-matrix interactions 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 mechanisms of cell-matrix interactions during the growth and progression of human neoplasms.