Heparanase-1 activity in pancreatic cancer patient serum decreases after gemcitabine therapy

Abstract

Introduction: Heparanase-1 (HPR) is an endoglycosidase that specifically degrades the heparan sulfate side chains of proteoglycan, a chief component of the extracellular matrix (ECM). HPR plays an important role in tumor metastases. HPR expression is increased in up to 70% of pancreatic cancer patients and correlates with a shorter survival time. Since HPR expressed in tumor tissue can be secreted into blood, we sought to determine if HPR expression in tumor tissue resulted in increased HPR activity in the serum of pancreatic cancer patients. We also evaluated the serum of pancreatic cancer patients for HPR activity before and after gemcitabine therapy as a potential indicator of tumor response to chemotherapy. Methods: Six blood samples were collected from pancreatic cancer patients before and after chemotherapy. Serum HPR activity was measured using a novel ELISA and compared against a standard (activity of purified HPR). Serum samples from 36 pancreatic cancer patients who did not receive chemotherapy were also tested for HPR activity. Serum samples from 18 healthy volunteers were run as negative controls. Data was analyzed using ANOVA to determine statistical significance. Results: HPR activity in the serum samples of pancreatic cancer patients was increased approximately 3-fold, compared to that in the serum of healthy donors. HPR activity decreased in the serum of all 6 patients who received gemcitabine by 2 weeks after initiation of chemotherapy (p < 0.01). Conclusion: A novel ELISA was used to quantitate serum HPR activity in pancreatic cancer patients. HPR activity was markedly increased in the serum of pancreatic cancer patients, but decreased after initiation of chemotherapy. Serum HPR levels may potentially be used as a marker of tumor response to adjuvant treatment.