Macrophage infiltration and growth of sarcoma clones expressing different amounts of monocyte chemotactic protein/JE.
Tumor-derived chemotactic factors (TDCF) have been identified and thought to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of the TDCF molecularly identified as monocyte chemotactic protein/JE, by investigating murine sarcoma clones expressing different levels of MCP/JE. The 1D3 clone derived from the B77 RSV-induced sarcoma expressed appreciable levels of MCP/JE mRNA and, concomitantly, chemotactic activity for mononuclear phagocytes. In contrast, the 5B11 clone from the same tumor had undetectable levels of MCP/JE transcripts and little or no chemotactic activity. The chemotactic activity of 1D3 cells was blocked by an appropriate specific antiserum. The in vitro growth rate of the 2 sarcoma lines was identical. Upon in vivo transplantation, the 1D3 clone showed a substantially higher level of tumor-associated macrophages (28.9%; range 21%-34%) than the 5B11 clone (16.6%; range 13%-20%). 5B11-induced tumors appeared earlier and grew faster than those induced by 1D3. The difference in growth rate and in macrophage infiltration between 1D3 and 5B11 clones was also evident upon transplantation into nude mice. These results are consistent with the hypothesis that TDCF, identified as MCP/JE, is one important determinant of macrophage infiltration in tumors.
Walter
S
S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bottazzi
B
B
Govoni
D
D
Colotta
F
F
Mantovani
A
A
D000818:Animals; D002449:Cell Aggregation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D001357:Sarcoma, Avian / Q000378:metabolism* / Q000473:pathology
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm