A close association between stem cell/progenitor cell and integrin expression www.selleckchem.com/products/bgj398-nvp-bgj398.html also has been implicated in the requirement of integrins in the endodermal differentiation of human embryonic stem cells.[32] Cholangiolocellular carcinomas are usually negative for histochemical mucin staining, having a diagnostic value to differentiate CoCC from CCC, but there are few reports concerning the relationship between histochemical mucin production and integrins. In our preliminary study, immunohistochemical expression of

MUC1, one of the mucin core proteins, was shown in more than 90% of CoCC and CCC cases (unpubl. data). In addition, MUC4 on the cell surface has been reported to potentiate proliferation and invasive properties of pancreatic tumor

cells by interfering with the accessibility of α2, α3 and α5 integrins to its ligands.[33] Poor mucin production in CoCC may be related to low malignant potential through integrin-mediated check details pathway. Our in vitro experiments using the KMCH-2 cell line derived from CHC showed that the mRNA levels of β6, β4 and α3 integrins increased in a 3-D culture system using a collagen gel matrix, which has been reported to induce glandular structure in vitro.[28] These results suggest that these integrins are inducible under different culture conditions and that integrin expression may be associated with the differentiation of CHC cells. In addition, it is interesting that the expression of these integrins on cultured CHC cells increased in the proliferating phase under the pre-confluent condition, suggesting a relationship between tumor cell proliferation and integrin expression. These results are consistent with the findings of a previous study, showing that there was a close association between β6 expression and cholangiocyte proliferation in the liver[18] and also a relationship between β4 expression and cancer cell proliferation in CCC, with medchemexpress involvement

in the prognosis.[26] This may be a reason why integrin expression is downregulated in CoCC, as it was evident in our collected cases that the CoCC proliferative activities evaluated by Ki-67 labeling indices were significantly lower than those in CCC (unpubl. data). An abundant stroma with characteristic dense fibrosis is known to be present in CoCC, but, to the best of our knowledge, there is no report on the investigation of ECM components in CoCC. In the present study, the aberrant and enhanced expression of fibronectin was demonstrated more frequently in HCC than in CCC and CoCC. However, although the connection between αvβ1/αvβ5 integrin and its extracellular ligand, vitronectin, in HCC has been implicated in addition to an adverse prognostic role,[34] the correlation between the expression of αvβ6 and its ligand, fibronectin, in CoCC, CCC and HCC was not indicated in the present study.