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Updated: Apr 15, 2026
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Deciphering the cellular source of tumor relapse identifies CD44 as a major therapeutic target in pancreatic
Maria Inés Molejon1, Juan Ignacio Tellechea1,2, Celine Loncle1
1Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.
Abstract:
It has been commonly found that in patients presenting Pancreatic Ductal Adenocarcinoma (PDAC), after a period of satisfactory response to standard treatments, the tumor becomes non-responsive and patient death quickly follows. This phenomenon is mainly due to the rapid and uncontrolled development of the residual tumor. The origin and biological characteristics of residual tumor cells in PDAC still remain unclear. In this work, using PDACs from patients, preserved as xenografts in nude mice, we demonstrated that a residual PDAC tumor originated from a small number of CD44+ cells present in the tumor. During PDAC relapse, proliferating CD44+ cells decrease expression of ZEB1, while overexpressing the MUC1 protein, and gain morphological and biological characteristics of differentiation. Also, we report that CD44+ cells, in primary and residual PDAC tumors, are part of a heterogeneous population, which includes variable numbers of CD133+ and EpCAM+ cells. We confirmed the propagation of CD44+ cells in samples from cases of human relapse, following standard PDAC treatment. Finally, using systemic administration of anti-CD44 antibodies in vivo, we demonstrated that CD44 is an efficient therapeutic target for treating tumor relapse, but not primary PDAC tumors. We conclude that CD44+ cells generate the relapsing tumor and, as such, are themselves promising therapeutic targets for treating patients with recurrent PDAC.
Insights
Residual tumor cells in Pancreatic Ductal Adenocarcinoma (PDAC) originate from CD44+ cells. Targeting CD44+ cells offers a promising strategy for treating recurrent PDAC, not primary tumors.
Area of Science:
- Oncology
- Cancer Biology
- Immunotherapy
Background:
- Pancreatic Ductal Adenocarcinoma (PDAC) often becomes resistant to treatment, leading to rapid relapse and patient mortality.
- The cellular origin and biological traits of residual PDAC tumors remain poorly understood, hindering effective treatment strategies.
Purpose of the Study:
- To investigate the cellular origin of residual PDAC tumors and identify potential therapeutic targets for recurrent disease.
- To characterize the biological changes in residual tumor cells during PDAC relapse.
Main Methods:
- Utilized patient-derived PDAC xenografts in nude mice for experimental models.
- Employed cell surface marker analysis (CD44, CD133, EpCAM) to identify and isolate tumor cell populations.
- Administered anti-CD44 antibodies systemically in vivo to assess therapeutic efficacy.
Main Results:
- Residual PDAC tumors arise from a small subpopulation of CD44+ cells within the primary tumor.
- During relapse, CD44+ cells exhibit altered gene expression (decreased ZEB1, increased MUC1) and gain differentiated characteristics.
- CD44+ cells are confirmed to drive tumor propagation in human relapse samples.
- Systemic anti-CD44 antibody treatment effectively targeted relapsed tumors but not primary PDAC.
Conclusions:
- CD44+ cells are the key progenitors of relapsing PDAC tumors.
- Targeting CD44 represents a promising therapeutic strategy for managing PDAC recurrence.
- CD44+ cells are a viable therapeutic target for patients with recurrent PDAC.
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