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Updated: Jul 5, 2026
Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer
Amit Verma1, Sushovan Guha, Parmeswaran Diagaradjane
1Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Purpose:
Tissue transglutaminase (TG2) is a multifunctional protein that is implicated in development of drug resistance and metastasis. Therefore, we examined therapeutic targeting of TG2 for inhibiting growth and metastasis of in vivo growing pancreatic ductal adenocarcinoma (PDAC) in nude mice.
Experimental Design:
We implanted Panc-28 pancreatic cancer cells to induce orthotopic PDAC tumors in nude mice and determined the efficacy of liposomal TG2 small interfering RNA (siRNA) either alone or in combination with gemcitabine.
Results:
We show that down-regulation of endogenous TG2 by siRNA could effectively block the growth of PDAC. Moreover, down-regulation of TG2 significantly enhanced the therapeutic efficacy of gemcitabine against PDAC and inhibited metastatic spread of the disease. The antitumor activity was related to inhibition of proliferation, angiogenesis, and Akt phosphorylation.
Conclusion:
siRNA-mediated down-regulation of TG2 represents a promising therapeutic approach for improved treatment of PDAC.
Insights
Targeting tissue transglutaminase (TG2) with small interfering RNA (siRNA) effectively blocks pancreatic ductal adenocarcinoma (PDAC) growth and metastasis. This approach enhances gemcitabine therapy, offering a promising strategy for PDAC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Tissue transglutaminase (TG2) is a key protein linked to drug resistance and metastasis in cancers.
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options.
Purpose of the Study:
- To investigate the therapeutic potential of targeting TG2 for inhibiting PDAC growth and metastasis.
- To evaluate the efficacy of TG2 small interfering RNA (siRNA) in an in vivo PDAC model.
Main Methods:
- Orthotopic implantation of Panc-28 pancreatic cancer cells in nude mice.
- Treatment with liposomal TG2 siRNA, alone and in combination with gemcitabine.
Main Results:
- TG2 down-regulation via siRNA effectively inhibited PDAC tumor growth.
- TG2 inhibition significantly enhanced gemcitabine's efficacy against PDAC.
- Therapeutic effects included reduced proliferation, angiogenesis, and Akt phosphorylation, alongside inhibited metastasis.
Conclusions:
- siRNA-mediated TG2 down-regulation is a promising strategy for enhancing PDAC treatment.
- Targeting TG2 offers a novel therapeutic avenue for combating pancreatic cancer progression and metastasis.
