Increased blood clotting, microvascular density, and inflammation in eotaxin-secreting tumors implanted into mice.
An important theme that is emerging in cancer research is the interaction between tumor cells and the host stroma. Because many types of human cancer are infiltrated by eosinophils that are believed to mediate an anti-tumor cytotoxic effect, we developed and studied a transfected B16 murine melanoma cell line that secretes high levels (510 pg/ml/100,000 cells/day) of eotaxin, a chemokine that recruits and activates primarily eosinophils. Here we report that there was increased inflammation (eosinophils, mast cells, mononuclear cells), blood clotting, and microvascular density within the tumors produced by subcutaneous implants of eotaxin-secreting tumor cells in 10 C57BL/6 compared to tumors produced by wild-type tumor cells. The extensive blood clotting in the eotaxin-transfected tumors was associated with significantly decreased blood flow to the tumors as measured by magnetic resonance imaging [(mean maximum signal enhancement of eotaxin-secreting tumors, 147 +/- 57 (n = 7) compared to 202 +/- 36 signal enhancement units (n = 8) for the wild-type melanoma cells; P = 0.04 by two-tailed, unpaired t-test]. Surprisingly, there was no significant difference between the growth rates or mean masses of the eotaxin-secreting tumors (750 +/- 280 mg, n = 10) and the wild-type tumors (780 +/- 290, n = 10) after 20 days of growth in vivo, despite the significantly slower growth rate in vitro of the eotaxin-secreting tumor cells. We conclude that eotaxin and the resultant tumor-infiltrating inflammatory cells are not likely to mediate a significant anti-tumor effect in vivo. Instead, elevated eotaxin is associated with increased inflammation, microvascular density, and blood clotting. Thus, eotaxin and eosinophils may play a more complex role in modulating the growth of tumors than the simple, anti-tumor cytotoxic effect that has been previously proposed.
Samoszuk
Michael
M
Pathology Department, University of California, Irvine, Building 10, Route 40, 101 The City Drive, Orange, CA 92868, USA. msamoszu@uci.edu.
Deng
Tom
T
Hamamura
Mark J
MJ
Su
Min-Ying
MY
Asbrock
Nicholas
N
Nalcioglu
Orhan
O
D000818:Animals; D001777:Blood Coagulation; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism*; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000473:pathology*; D014162:Transfection
C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil