acid-phosphatase and Carcinoma--Neuroendocrine

A 58-year-old man was revealed to have multiple liver tumors with elevated prostatic acid phosphatase (PAP) during a medical examination. The tumors were of neuroendocrine nature, but no abnormal findings were obtained in other organs in which neuroendocrine tumors develop frequently. Repeated transarterial embolization was partially effective. However, the tumors became resistant to the therapy three years later, continued growing and ruptured. Autopsy disclosed neuroendocrine tumors in the pancreas, which were immunohistologically positive for PAP. Neuroendocrine tumors of the pancreas and liver producing PAP are rare; this case is reported with a review of literature.

Topics: Acid Phosphatase; Carcinoma, Neuroendocrine; Fatal Outcome; Humans; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Prostate

Because prostate cancer is, in its early stages, an androgen-dependent pathology, treatments aiming at decreasing testosterone plasma concentration have been developed for many years now. However, a significant proportion of patients suffer a relapse after a few years of hormone therapy. The androgen-independent stage of prostate cancer has been shown to be associated with the development of neuroendocrine differentiation. We previously demonstrated that neuroendocrine prostate cancer cells derived from LNCaP cells overexpress CaV3.2 T-type voltage-dependent calcium channels. We demonstrate here using prostatic acid phosphatase as a marker of prostate secretion and FM1-43 fluorescence imaging of membrane trafficking that neuroendocrine differentiation is associated with an increase in calcium-dependent secretion which critically relies on CaV3.2 T-type calcium channel activity. In addition, we show that these channels are expressed by neuroendocrine cells in prostate cancer tissues obtained from patients after surgery. We propose that CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors, could participate in the progression of the disease toward an androgen-independent stage.

Topics: Acid Phosphatase; Androgens; Biomarkers, Tumor; Calcium; Calcium Channels, T-Type; Carcinoma, Neuroendocrine; Cell Differentiation; Cell Line, Tumor; Growth Substances; Hormone Replacement Therapy; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Testosterone; Up-Regulation