Abstract
Pancreatic cancer (PC) is one of the deadliest cancers and remains a major challenge due to its invasive and metastatic nature. Increased levels of CCR5 and CCL5 have established indicators for disease status in various cancers, including PC. However, their role in invasion and metastasis of PC is not known. Here we conducted immunohistochemistry of PC tissues and found elevated epithelial staining for CCR5 and CCL5 in metastatic PC tissues compared to non-neoplastic. In vitro experiments, such as flow cytometry, immunofluorescence and western blotting with human PC cell lines (AsPc-1, BxPc-3 and MIA PaCa-2), showed higher expression levels of CCR5. The CCL5 activation of PC cells expressing CCR5 increased their invasive potential, while treatment with CCR5 inhibitor maraviroc inhibited the CCL5 activation. CCL5 induced proliferation of PC cells was mediated through F-actin polymerization, while there was marked reduction when the cells were treated with maraviroc. The direct interaction of CCR5 with CCL5 was verified using a calcium mobilization assay. Taken together, our results demonstrate that CCR5 and CCL5 are potential markers for metastatic PC cancer, and their interaction leads to the increased PC cell invasion. Thus, blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression.
Highlights
Pancreatic adenocarcinoma is one of the most deadly cancers for solid malignancies and remains a major challenge in oncology because of its poor response to chemotherapy and radiation as well as its invasive and metastatic nature[1]
The poorly differentiated tissues had high expression of CCR5 and CCL5.We further quantify the expression level in tissue using the Histo Quest software; hematoxylin staining was used as a master marker for cell identification on the basis of nuclear detection
To the importance of chemokine study in tumor cells, we further extend CCR5/CCL5 interaction in selected Pancreatic cancer (PC) cell lines
Summary
Pancreatic adenocarcinoma is one of the most deadly cancers for solid malignancies and remains a major challenge in oncology because of its poor response to chemotherapy and radiation as well as its invasive and metastatic nature[1]. Chemokines are proinflammatory chemoattractant cytokines that function primarily in leukocyte trafficking and other biological activities, such as development, angiogenesis, and hematopoiesis[8] Chemokines bind to their cognate receptors, most of which belong to the G-protein coupled receptor family, and are expressed on endothelial cells and lymphocytes. In addition to their role in several pathological conditions, it www.nature.com/scientificreports/. Among the receptors of CCL5, its interaction with CCR5 was very well established and elucidated in tumor progression and recruitment of tumor infiltration leukocytes in several cancer types. Its expression on cancer cells, along with CCL5 has found to play an important role in cancer progression and metastasis. CCR5/CCL5 participation in activating invasion and metastasis of PC has not been reported yet
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