title: Direct TGF-β1 signaling between activated platelets and pancreatic cancer cells primes cisplatin insensitivity.
abstract: The exact mechanisms underlying chemotherapy insensitivity in pancreatic cancer remain largely unclear. The dynamic cross talk between tumors and their microenvironment is an important determinant of cancer chemosensitivity. However, whether additional signals provided during the intravascular transit of tumor cells affect the sensitivity of pancreatic cancer cells to chemotherapy is unknown. We have found that activated platelet-cancer cell interactions are sufficient to prime cisplatin (CDDP) insensitivity in pancreatic cancer cells. Activated platelet-derived TGF-β1 rather than direct platelet-tumor cell contacts stimulates PI3K/Akt and MEK/Erk signaling in pancreatic cancer cells, resulting in reduction of CDDP sensitivity in these cells. Therefore, the platelet-tumor cell interactions and the relevant signaling pathways that prime CDDP insensitivity may be potential targets for adjuvant chemotherapy for pancreatic cancer.
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu Daping, Chongqing 400042, P.R., China.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Lan
authors.forename: Menggang
authors.initials: M
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Baoling
authors.initials: B
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015539:Platelet Activation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D053773:Transforming Growth Factor beta1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D002945:Cisplatin