Interleukin 6 gene-transfected mouse mammary adenocarcinoma: tumour cell growth and metastatic potential.
Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BALB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an in vitro increased growth rate compared with that of TSA cells transfected with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell colonies consisted mainly of fusiform cells and TSA-neo colonies of polygonal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA-IL6 cells gave rise to tumours that grew significantly slower than TSA-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fascicular pattern of growth, associated with a very scanty macrophage infiltrate. S.c. TSA-IL6 tumours were significantly less metastatic than TSA-neo tumours. By contrast, following intravenous (i.v.) challenge, TSA-IL6 cells produced 5-7 times more lung metastases than TSA-neo cells. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage infiltrate and a rich vascularization. The high in vitro TSA-IL6 cell growth rate is attributable to the IL6-induced production of growth factors, some of which possess heparin-binding properties, such as amphiregulin. The differences in vascularization and macrophage infiltrate may underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth of i.v. metastasis.
Di Carlo
E
E
Istituto di Patologia Umana e Medicina Sociale, Università G. D'Annunzio, Italy.
Modesti
A
A
Castrilli
G
G
Landuzzi
L
L
Allione
A
A
de Giovanni
C
C
Musso
T
T
Musiani
P
P
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D000818:Animals; D002455:Cell Division; D005260:Female; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D015850:Interleukin-6