Specific enhanced expression of platelet-derived endothelial cell growth factor in submucosa of human colorectal cancer.
OBJECTIVE
Platelet-derived endothelial cell growth factor, identified to be an angiogenic factor, has been implicated in metastases of colorectal cancer. This study aimed to clarify the role and localization of platelet-derived endothelial cell growth factor associated with human colorectal cancer invasion.


METHODS
Thirty-two patients with colorectal cancer who had undergone surgery were analyzed. Platelet-derived endothelial cell growth factor enzyme activities in the colorectal cancer specimens were measured. Cells that expressed platelet-derived endothelial cell growth factor were identified and localized by immunohistochemical analysis with anti-human platelet-derived endothelial cell growth factor antibody and by in situ hybridization with specific RNA probe.


RESULTS
Platelet-derived endothelial cell growth factor enzyme activity increased significantly in cancer tissues compared with normal colonic mucosa at various distances from the cancer. Immunohistochemical analysis and in situ hybridization demonstrated platelet-derived endothelial cell growth factor expression in stromal macrophages and fibroblasts located in cancer tissues and surrounding noncancerous tissues, although the tumor cells and normal colonic mucosa were negative. The value of platelet-derived endothelial cell growth factor expression was highest at the border of the colorectal cancer (35.3 +/- 8.9 percent), followed by the cancer nest (15.2 +/- 9.2 percent) and normal mucosa (7.7 +/- 3.4 percent). In the border area, the highest value of platelet-derived endothelial cell growth factor expression was observed in the submucosa (35.3 +/- 8.9 percent), followed by the muscular propria (21.9 +/- 7.7 percent) and the subserosa (14.9 +/- 5.5 percent).


CONCLUSIONS
Stromal macrophages and fibroblasts are responsible for elevated platelet-derived endothelial cell growth factor activity in colorectal cancer. The significance of enhanced expression of platelet-derived endothelial cell growth factor in the submucosa at the cancer border remains unclear. Cancer stroma may be an important factor for cancer angiogenesis and may serve as a treatment target through specific modulation of angiogenic factors.
Nozawa
Tadashi
T
Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
Enomoto
Takumo
T
Koshida
Yoshitomo
Y
Sato
Yuichi
Y
Kuranami
Masaru
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000032:analysis; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007413:Intestinal Mucosa / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D007564:Japan; D008264:Macrophages / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015347:RNA Probes; D017154:Stromal Cells / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D013939:Thymidine Phosphorylase / Q000032:analysis / Q000235:genetics / Q000502:physiology
D043925:Angiogenesis Inducing Agents; D015347:RNA Probes; D013939:Thymidine Phosphorylase