Differential expression of intracellular apoptotic signaling molecules in tumor and tumor-infiltrating lymphocytes during development of invasion and/or metastasis of gastric carcinoma.
The presence and functional status of intracellular expression of caspase 8, caspase 10, cFLIP, caspase 3, survivin, and NF-kappaB was investigated in permeabilized tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma (N = 20) from primary locus, metastatic gastric carcinoma (N = 22) from malignant ascites, and benign gastric mucosa (N = 20) for the control. The quantitative analysis was based on the percentage of positive cells by a flow cytometry. The results showed that the six intracellular molecules were constitutively expressed in primary and metastatic carcinomas as well as normal epithelium in nearly all the patients. In particular, metastatic carcinoma revealed to significantly overexpress these molecules. In the analysis of TIL, the expression of these six molecules could usually be observed in carcinoma and normal epithelium. There was aberrant expression of these molecules in immune TIL within metastatic carcinoma nests. Taken together, the results showed the significantly different expression of the signaling molecules in both tumor and TIL between primary and metastatic carcinoma nests. Increased expression of cFLIP, survivin, and NF-kappaB in carcinoma might play an important role in hindering an intracellular apoptotic process, followed by accelerating the cancer invasion and/or metastasis.
Koyama
Shohei
S
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Ibaraki 305-8575 Japan. s-koyama@md.tsukuba.ac.jp
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin
C107489:BIRC5 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000077022:Survivin; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; C506438:CASP10 protein, human