Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer.
Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(-)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(-)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+)/VEGF-189(-) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189.
Tokunaga
T
T
Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Nakamura
M
M
Oshika
Y
Y
Abe
Y
Y
Ozeki
Y
Y
Fukushima
Y
Y
Hatanaka
H
H
Sadahiro
S
S
Kijima
H
H
Tsuchida
T
T
Yamazaki
H
H
Tamaoki
N
N
Ueyama
Y
Y
D000704:Analysis of Variance; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary*; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000378:metabolism*; D019699:Thrombospondins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2
D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019700:Thrombospondin 1; D019699:Thrombospondins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2; C467484:VEGFA protein, human