EFFECT OF RECONSTITUTED BASEMENT-MEMBRANE COMPONENTS ON THE GROWTH OFA PANEL OF HUMAN TUMOR-CELL LINES IN NUDE-MICE

Previous reports have indicated that reconstituted basement membrane ( matrigel), when co-injected with either established or primary human t umour cells, can improve the growth of subcutaneous xenografts in nude mice. The human adenocarcinoma cell lines A549, SW480, and WiDr, and the human fibrosarcoma cell line HT1080scc2 exhibit varying degrees of tumourigenicity in nude mice. All these lines showed increased tumour igenicity and/or growth rate, together with a change towards a more di fferentiated tissue morphology, when co-injected with matrigel into nu de mice. Experiments using A549 cell line have indicated that the effe ct of matrigel is concentration-dependent and that increased growth ra te is not maintained when xenografts grown with matrigel are passaged into further mice. These results strongly suggest that increased tumou r growth results from the improved growth conditions afforded by matri gel, rather than from the selection of subpopulations of the most tumo urigenic cells. Increased growth of intracaecal tumours arising from t he co-injection of SW480 cells with matrigel, indicate a possible use for matrigel in the development of more relevant animal models using t he orthotopic site. Purified laminin significantly increased the growt h of sc tumours resultant from co-injection with either WiDr or A549 c ells, whereas collagen IV or laminin with entactin showed no such effe ct. A role for free laminin in the stimulation of cell growth in the a bsence of an intact basement membrane is discussed.