Background: The destruction of the basement membrane (BM) is the first step in cancer cell invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct alpha(IV) chains: alpha1(IV) to alpha6(IV). The loss of alpha5/alpha6(IV) chains from the epithelial BM at the early stage of cancer cell invasion has been reported in several cancers. However, the expression of alpha5/alpha6(IV) chains in esophageal squamous cell carcinoma (ESCC) remains unclear.
Methods: The expression of alpha(IV) chains in 116 resected ESCC specimens was immunohistochemically examined. The role of alpha6(IV) chain was assessed in ESCC cell lines by short interfering RNA (siRNA).
Results: In intraepithelial carcinoma, the alpha5/alpha6(IV) chains were stained in a continuous linear pattern in the BM. In some cases of ESCC with the invasion beyond the lamina propria, the alpha5/alpha6(IV) chains were lost in the BM zone surrounding the cancer cell nests, but in other cases they remained. In the former, the disease-free survival and overall survival were significantly better than in those with the latter. The down-regulation of alpha6(IV) chain expression by siRNA revealed a slight increase of cancer cell invasiveness.
Conclusions: The evaluation of alpha5/alpha6(IV) chains may be a useful marker for determining tumor cell properties, as a prognostic factor, in patients with ESCC.