Increased expression of S100A6 at the invading fronts of the primary lesion and liver metastasis in patients with colorectal adenocarcinoma

Abstract

Two members of the S100 gene family, S100A6 and S100A4 have been suggested to be associated with cancer invasion and metastasis. To study their involvement in the malignancy of human colorectal adenocarcinoma, we examined the protein expression levels of S100A6 and S100A4 in the primary colorectal adenocarcinoma (T) and paired adjacent normal colorectal mucosa (N) from 12 cases, quantitatively by Western blot analysis. In 11 of 12 and seven of 12 cases, S100A6 and S100A4 expression levels were higher in T than in N, respectively. Average S100A6 level in T was significantly higher than in N (about × 2.3;P= 0.001), whereas average S100A4 level in T was not. When S100A6 expression levels in three sets of matched samples of primary colorectal adenocarcinoma (T) and liver metastasis (M) were examined, S100A6 levels were higher in M than in T in two of three cases. Immunohistochemical analysis using monoclonal anti-S100A6 antibody showed that 23 of 42 (55%) primary colorectal adenocarcinoma and 15 of 16 (94%) liver metastasis specimens were positively stained. S100A6 immunostaining of primary colorectal adenocarcinomas was significantly more intense in the invading fronts with structural atypia than in central portions with glandular structure (P< 0.0001), whereas Ki-67 staining (a growth marker) was similar in these two portions. Interestingly, S100A6 and Ki-67 immunostaining patterns in liver metastases were also the same as in primary lesions. These results suggest that S100A6 is involved in the invasive process of human colorectal adenocarcinomas and that S100A6 expression levels decrease when carcinoma cells form glandular structure again at the central portions of metastatic nodules. © 2000 Cancer Research Campaign

S100A4 (p9Ka) protein in colon carcinoma and liver metastases: association with carcinoma cells and T-lymphocytes

“…However, the result was found not to be statistically significant (Komatsu et al, 2001). Whilst it is possible that S100A4 protein was also elevated in the adjacent normal tissue, it is more likely that this result arises from variability in the levels of S100A4 in the carcinoma specimens as measured by Western blotting, due to the presence of S1004 in infiltrating lymphocytes, as found in the present study.…”

“…When the S100A4 levels in epithelial cells were compared immunocytochemically (Table 2), the proportion of specimens exhibiting epithelial staining for S100A4 was more strongly significantly different between carcinomas and normal colon (P=0.0016, Fisher exact test) than when specimens were compared using the quantitative RT -PCR technique (P=0.05, Fisher exact test). The quantitative RT -PCR technique, like the Western blotting used by Komatsu et al (2001) does not distinguish between staining of epithelial and infiltrating host cells.…”

S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

“…The only other published study, which to our knowledge examined the effect of S100A6 on motility, showed a decrease in the motility of one of three osteosarcoma cell lines after adenoviral-mediated overexpression of S100A6 (Luu et al, 2005). Interestingly in osteosarcoma, a trend was observed between decreased metastasis and increased S100A6 staining, contrasting the findings in melanoma and colorectal cancer (Maelandsmo et al, 1997;Komatsu et al, 2000). Whether S100A6 contributes to pancreatic cancer cell motility through interaction with annexin 2 is not yet clear.…”

“…Although S100A6 overexpression in pancreatic and other cancers, including gastric (Yang et al, 2007), thyroid (Brown et al, 2006), breast (Cross et al, 2005) and colorectal (Komatsu et al, 2000) has been documented, its precise role in cancer is not known. In pancreatic cancer, the expression of S100A6 appears to correlate with aggressive disease in that high levels of tumour S100A6 are associated with poorer outcome (Vimalachandran et al, 2005), whereas pancreatic cancer cells depleted of S100A6 are less invasive (Ohuchida et al, 2005).…”

“…In pancreatic cancer, the expression of S100A6 appears to correlate with aggressive disease in that high levels of tumour S100A6 are associated with poorer outcome (Vimalachandran et al, 2005), whereas pancreatic cancer cells depleted of S100A6 are less invasive (Ohuchida et al, 2005). A link between S100A6 and colon cancer invasion has also been suggested by the observation that increased expression of S100A6 is found at the leading edges of colon cancer tissues (Komatsu et al, 2000). However, the molecular mechanism responsible for these effects has not been characterised.…”