Locally applied TCP inhibits tumor growth via possible activation of macrophages.
The aim of this study was to investigate whether beta-tricalcium phosphate (TCP) inhibits cancer growth, because TCP, a widely used bone replacement material, is known to attract immune cells. Human colon cancer (WiDr) cells were subcutaneously injected on the backs of nude mice, and tumor growth was observed. Seven days after the injection, five animals were implanted with TCP at the tumor sites, five animals were treated by a direct application of 0.12 mg cisplatin at the sites, and four animals were not treated, as a control. Tumor size on the 43rd day of implantation was 1173 mm(3) in the TCP group and was smaller than that in the control, 1621 mm(3). This inhibition was comparable to that with cisplatin. Furthermore, tumor-growing rate in the TCP group was significantly lower than that in the control group. Histopathological examination of the tumors showed migration of macrophages only in the TCP group, with TCP particles remaining at the implantation loci. There were no between-group differences in neutrophil infiltration and angiogenesis. In another series of in vitro experiments, a concentration-dependent increase in luminol chemiluminescence was observed in isolated human peripheral neutrophils incubated with TCP, and the chemiluminescence due to phagocytosis of opsonized zymosan in the presence of TCP occurred with a lower level of TCP than when the chemiluminescence was due to TCP alone. These results suggest that subcutaneously implanted TCP inhibits tumor growth of implanted WiDr cells, and that the activation by TCP of macrophages plays a role in that inhibition.
Naito
Yukiko
Y
Laboratory of Pharmacology, Hatano Research Institute, Food and Drug Safety Center, Ochiai 729-5, Hadano, Kanagawa 257-8523, Japan. naito.yuki@fdsc.or.jp
Nagata
Tomoko
T
Tachibana
Shigehiro
S
Okimoto
Mari
M
Ohara
Naoki
N
Hakamatsuka
Yasuharu
Y
Cheng
Jinyan
J
D000818:Animals; D000970:Antineoplastic Agents; D001672:Biocompatible Materials / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D049449:Luminescence; D008165:Luminol; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000187:drug effects; D015054:Zymosan / Q000737:chemistry
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D002130:Calcium Phosphates; D009895:Opsonin Proteins; C485817:beta-tricalcium phosphate; D008165:Luminol; D015054:Zymosan