Related Experiment Video
Updated: May 12, 2026
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Direct TGF-β1 signaling between activated platelets and pancreatic cancer cells primes cisplatin insensitivity
Hongxu Chen1, Xiang Lan, Menggang Liu
1Department of Hepatobiliary Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu Daping, Chongqing 400042, P.R., China.
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.
Insights
Activated platelets prime pancreatic cancer cells for chemotherapy insensitivity via TGF-β1 signaling. This interaction, involving platelet-derived TGF-β1, reduces sensitivity to cisplatin, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Cancer Biology
- Translational Research
Background:
- Pancreatic cancer exhibits significant chemotherapy insensitivity, hindering effective treatment.
- Tumor microenvironment interactions critically influence cancer cell chemosensitivity.
- The role of signals during tumor cell intravascular transit in chemotherapy response is largely unknown.
Purpose of the Study:
- To investigate if intravascular signals, specifically platelet-cancer cell interactions, affect pancreatic cancer cell sensitivity to chemotherapy.
- To elucidate the mechanisms by which platelet interactions might induce chemotherapy insensitivity.
Main Methods:
- Utilized in vitro models of pancreatic cancer cells and activated platelets.
- Assessed the impact of platelet-cancer cell interactions on sensitivity to cisplatin (CDDP).
- Investigated the role of platelet-derived transforming growth factor-beta 1 (TGF-β1) and downstream signaling pathways (PI3K/Akt, MEK/Erk).
Main Results:
- Activated platelet-cancer cell interactions are sufficient to induce cisplatin (CDDP) insensitivity in pancreatic cancer cells.
- Platelet-derived TGF-β1, not direct cell contact, activates PI3K/Akt and MEK/Erk signaling in cancer cells.
- Activation of these pathways leads to a significant reduction in CDDP sensitivity.
Conclusions:
- Platelet-cancer cell interactions, mediated by TGF-β1, represent a novel mechanism for chemotherapy insensitivity in pancreatic cancer.
- Targeting platelet-derived TGF-β1 and associated signaling pathways may offer new strategies for overcoming cisplatin resistance in pancreatic cancer.
- These findings highlight the importance of the tumor microenvironment during metastasis in shaping treatment response.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:16TGF - β Signaling Pathway