Transforming growth factor-beta1 induced hepatocyte apoptosis--a possible mechanism for growth of colorectal liver metastasis.
The mechanisms of colonization and growth of metastatic liver tumors from colorectal cancers remain obscure. Forty-three resected colorectal metastatic liver tumors with surrounding livers were evaluated for apoptotic index (AI), proliferation index (PI), and immunohistochemical expressions of TGF-beta1. TGF-beta receptor II, Fas, and Fas-ligand. All the parameters were significantly higher in the peri-tumoral livers than in the tumors with the exception of PI, which was significantly high in tumors. Enhanced TGF-beta1 expression was noticed at the interface between the metastatic tumor and the adjacent liver parenchyma. The AIs of hepatocytes in the TGF-beta1-positive areas (8.7 +/- 7.5%, n = 43) were significantly higher when compared with those in the TGF-beta1-negative areas (2.4 +/- 4.5%, n = 42) (p < 0.001). However, the same kind of correlation could not be found in metastatic tumors. The enhanced expression of TGF-beta1 and hepatocyte apoptosis in the peri-tumoral liver parenchyma may suggest that TGF-beta1 plays a substantial role in the development of colorectal liver metastasis.
Hayashi
Hikota
H
Second Department of Surgery, Shimane Medical University, Izumo, Japan. hikota@masumi.shimane.med.or.jp
Kohno
Hitoshi
H
Ono
Takashi
T
Yamanoi
Akira
A
Dhar
Dipok K
DK
Ueda
Shuhei
S
Rahman
Mohammad A
MA
Kubota
Hirofumi
H
Nagasue
Naofumi
N
D000368:Aged; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D019014:fas Receptor / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018125:Receptors, Transforming Growth Factor beta; D019014:fas Receptor