Angiogenesis and growth of murine colon carcinoma are dependent on infiltrating leukocytes

We determined whether the angiogenesis and growth of murine colon carcinoma s growing in the wall of the cecum is dependent on infiltrating leukocytes. Syngeneic BALB/c or SCID mice were treated with a myelosuppressive, maxima lly tolerated dose of doxorubicin. Parental or multidrug resistant CT-26 co lon carcinoma cells were implanted into the cecal wall 3 days after the sec ond intravenous injection of doxorubicin. Control mice developed large, wel l-vascularized tumors, whereas doxorubicin-pretreated mice did not. Intrave nous injection of spleen cells from normal BALB/c or SCID mice one day prio r to tumor cell implantation reversed the decreased vascularity and tumorig enicity. The production of proangiogenic molecules and microvessel density in tumors directly correlated with the number of infiltrating leukocytes, s uggesting that tumor-infiltrating leukocytes are essential to angiogenesis of murine colon carcinomas.