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Proceedings Paper

Extracellular matrix composition and rigidity regulate invasive behavior and response to PDT in 3D pancreatic tumor models
Author(s): Gwendolyn Cramer; Hamid El-Hamidi; Seyedehrojin Jafari; Dustin P. Jones; Jonathan P. Celli
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Paper Abstract

The composition and mechanical compliance of the extracellular matrix (ECM) have been shown to serve as regulators of tumor growth and invasive behavior. These effects may be particularly relevant in tumors of the pancreas, noted for a profound desmoplastic reaction and an abundance of stroma rich in ECM. In view of recent progress in the clinical implementation of photodynamic therapy (PDT) for pancreatic tumors, in this report we examine how ECM composition and rheological properties impact upon invasive behavior and response to PDT in 3D multicellular pancreatic tumor spheroids in ECM environments with characterized rheological properties. Tumor spheroids were cultured initially in attachment-free conditions to form millimeter-sized spheroids that were transplanted into reconstituted ECM microenvironments (Matrigel and Type I Collagen) that were characterized using bulk oscillatory shear rheology. Analysis of growth behavior shows that the soft collagen ECM promoted growth and extensive invasion and this microenvironment was used in subsequent assessment of PDT and chemotherapy response. Evaluation of treatment response revealed that primary tumor nodule growth is inhibited more effectively with PDT, while verteporfin PDT response is significantly enhanced in the ECM-infiltrating populations that are non-responsive to oxaliplatin chemotherapy. This finding is potentially significant, suggesting the potential for PDT to target these clinically problematic invasive populations that are associated with aggressive metastatic progression and chemoresistance. Experiments to further validate and identify the mechanistic basis of this observation are ongoing.

Paper Details

Date Published: 5 April 2016
PDF: 7 pages
Proc. SPIE 9694, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 96940J (5 April 2016); doi: 10.1117/12.2213843
Show Author Affiliations
Gwendolyn Cramer, Univ. of Massachusetts Boston (United States)
Hamid El-Hamidi, Univ. of Massachusetts Boston (United States)
Seyedehrojin Jafari, Univ. of Massachusetts Boston (United States)
Dustin P. Jones, Univ. of Massachusetts Boston (United States)
Jonathan P. Celli, Univ. of Massachusetts Boston (United States)


Published in SPIE Proceedings Vol. 9694:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
David H. Kessel; Tayyaba Hasan, Editor(s)

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