Pancreatic
adenocarcinoma is one of the most deadly
malignancies, and
endometrial cancer represents the most common gynecologic
cancer in the USA. Better understanding on the pathologic mechanisms and pathways is required for effective treatment of these
malignancies. Recently, human epididymis
protein 4 (HE4 or WFDC2), a secretory
glycoprotein, was found to be overexpressed in pancreatic and
endometrial cancers. In addition, studies have shown that HE4 overexpression in
endometrial cancer cell lines led to faster
cancer progression in a mouse subcutaneous model. These findings raise a question on the role(s) of secretory, extracellular HE4 in
cancer development. In the present study, we found that treatment of pancreatic and
endometrial cancer cell lines with purified, extracellular HE4
protein led to a significant increase in cell viability and proliferation. Moreover, extracellular HE4
protein was able to increase
DNA synthesis, and modulate the
mRNA and
protein levels of cell cycle marker
PCNA and cell cycle inhibitor p21. These effects appeared to be robust and sustainable and required a relatively low concentration of HE4
protein. The findings indicated the secreted, extracellular HE4 may carry some physiopathological functions. Via paracrine/endocrine actions, circulatory HE4 produced by malignant cells may contribute to pancreatic and
endometrial cancer progression and/or
metastasis.