Pancreatic stellate cell heterogeneity in cancer

Öhlund, Daniel, Handly-Santana, Abram, Elyada, Ela, Biffi, Giulia, Tuveson, David A. (2016) Pancreatic stellate cell heterogeneity in cancer. Pancreatology, 16 (3, Sup). S15. ISSN 1424-3903

URL: http://www.sciencedirect.com/science/article/pii/S...
DOI: 10.1016/j.pan.2016.05.055

Abstract

Introduction: Paracrine interactions between pancreatic stellate cells (PSCs) and tumor cells play key roles in pancreatic cancer tumorigenesis. However attempts to therapeutically target the PSCs have led to contradictory results, raising the possibility of diverse pathophysiological roles of these cells. Aims: The aim of this project is to gain a deeper understanding of the functional heterogeneity found in PSCs. Materials & methods: We have developed an organotypic co-culture system that allows us to study the interactions between tumor-derived organoids and PSCs in a three-dimensional matrix (Matrigel). Murine and human tissues have been used to validate our findings. Results: PSCs embedded in Matrigel acquire a quiescent phenotype, but become highly proliferative when co-cultured with tumor cells and differentiate into two distinct subtypes showing different phenotypic features. PSCs found in direct contact with tumor cells express smooth muscle actin (SMA), while PSCs that are more distant from the tumor cells show low SMA expression and gain a secretory phenotype. The secreted factors from this subtype of PSCs can activate certain pathways in tumor organoids important for proliferation and survival. We also show that these two subtypes are mutually exclusive and can both be found in vivo with similar spacial distribution as seen in the co-culture system. Conclusion: We have identified two subtypes of PSCs present in pancreatic cancer with potentially different pathophysiological functions. We believe that the outcome of trials targeting the PSCs will depend on which subtype that is preferentially affected by the treatment.

Item Type: Paper
Additional Information: Meeting abstract
Subjects: diseases & disorders > cancer > cancer types > pancreatic cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > pancreatic stellate cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > pancreatic stellate cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > pancreatic stellate cells
CSHL Authors:
Communities: CSHL labs > Tuveson lab
Depositing User: Matt Covey
Date Deposited: 23 Jun 2016 15:01
Last Modified: 23 Jun 2016 15:01
URI: http://repository.cshl.edu/id/eprint/32869

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