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Original Article

Evaluation of anti-metastatic effect of chitosan nanoparticles on
esophageal cancer-associated fibroblasts

Pravin D. Potdar, Aashutosh U. Shetti
Department of Molecular Medicine and Biology, Jaslok Hospital and Research Centre, Mumbai 400026, India.
Correspondence to: Dr. Pravin D. Potdar, Department of Molecular Medicine and Biology, Jaslok Hospital and Research Centre, Mumbai
400026, India. E-mail: ppravin012@gmail.com

Dr. Pravin D. Potdar’s present interest is to study molecular profiling of Circulating Tumor Cells (CTC), Circulating Tumor
DNA, Cancer Associated Fibroblasts and Cancer Stem Cells involved in metastatic process of cancers, and to see how this
process can be reverted back to normal by using innovated technologies which include nanotechnology and nanomedicine.

A B S T R AC T
Aim: Esophageal cancer is one of the major types of cancers, causing death of approximately 5% of all cancer deaths. This is
due, in large part, to both relatively ineffectual and unavailable treatment. In order to develop an effective treatment strategy
against esophageal cancer, it is important to target metastatic genes. In the present study, we have used a cancer-associated
fibroblast (CAF) cell line derived from culturing peripheral blood mononuclear cells from a metastatic esophageal cancer patient
to see whether chitosan nanoparticles (Ch-Np) treatment can modulate the metastatic phenotype of CAF cells by using various
cellular and molecular markers. Methods: A CAF cell line was developed from peripheral blood mononuclear cells (PBMC)
from a metastatic esophageal cancer patient. The cells were treated with 100 µg/mL of chitosan nanoparticle in vitro for the
morphological and oncogenic characteristic studies, along with the expression of various genes involved in process of tumor
development and metastasis. Techniques such as Light and Phase Contrast Microscopy, cell growth rate, Scratch metastatic assay,
and molecular profiling were carried out to see changes in CAF cells before and after Ch-Np treatment. Results: It was observed
that CAF cells grew in monolayer and had a doubling time of 25 ± 0.38 h. Morphologically, the cells had a fibroblastic appearance.
After treatment with 100 µg/mL of Ch-Np in vitro, there was an increased doubling time to 30 ± 0.83 h. Similarly, Scratch Assay
showed an inhibition in the metastatic property of these cells. These findings were confirmed with gene expression studies. It was
also observed that there was complete down-regulation of metastatic genes MMP1 and MMP9 and chemokines such as CXCR-4,
CXCR-7, CCR-5, and SDF-1, indicating that Ch-Np inhibited the metastatic characteristic of CAF cells. Conclusion: This study
has shown that there was an inhibition of metastatic properties of CAF cells after treatment with Ch-Np, suggesting that Ch-Np
can be a delivery system used for targeting cancer cells for treatment of esophageal cancer.
Key words: Cancer-associated fibroblast; molecular markers; metastasis; chitosan nanoparticle; anti-metastatic; metastatic genes

INTRODUCTION Tumor Growth Factor β (TGF-β) and Hepatocyte Growth
Factor (HGF) are the mediators released by CAFs. These
The tumor microenvironment plays a crucial role cause increased cell proliferation, more angiogenesis, and
in development and progression of cancers. The
[1]
microenvironment is mainly comprised of specialized reduced apoptosis. CAFs have been found to play an
stroma cells known as fibroblasts, also called cancer- important role in a variety of cancers, including breast,
associated fibroblast (CAF) or myofibriloblast. CAFs pancreatic, prostatic, and esophageal cancers. [2,3]
secrete various tumor promoting factors as well as
angiogenic factors which accelerates tumor growth. This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
Access this article online the author is credited and the new creations are licensed under the identical
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How to cite this article: Potdar PD, Shetti AU. Evaluation of anti-
metastatic effect of chitosan nanoparticles on esophageal cancer
DOI: associated fibroblasts. J Cancer Metasta Treat 2016;2:259-67.
10.20517/2394-4722.2016.25
Received: 17-05-2016; Accepted: 06-07-2016.

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 259