Release Subtitle: Researchers use 3D cell culture technology to recreate pancreatic cancer tissue in vitro with fibrotic components
Release Summary Text:
Pancreatic cancer is a deadly cancer characterized by prominent
fibrosis, which plays a crucial role in disease progression and
therapeutic resistance. Despite various efforts, experimental models to
date have generally failed to fully recapitulate the extent of fibrosis
in human tissue. Now, scientists at Okayama University, Japan, have
reported a new method that uses a 3D cell culture technique to generate
pancreatic cancer tissues in the laboratory with any given amount of
fibrosis.
Full text of release:
Pancreatic cancer is a life-threatening disease with very poor survival
rates in patients, and—despite various efforts—its treatment remains
challenging. This is because pancreatic cancer is characterized by the
presence of “fibrosis,” a pathological scarring process that occurs when
the physiological wound healing process goes awry. Thus, to tackle
pancreatic cancer, it is crucial to understand the mechanisms driving
fibrosis in detail. However, experimental models that are used to study
pancreatic cancer have not yet been able to fully replicate the extent
of fibrosis in human tissue.
To this end, researchers at Okayama University, Japan, including
Professor Mitsunobu R. Kano and Assistant Professor Hiroyoshi Y. Tanaka,
found a way to recreate pancreatic cancer tissue “in vitro” (in the
laboratory). Using a three-dimensional (3D) cell culture technique, they
devised a method to mix pancreatic cancer cells together with fibrotic
components to generate tissues that resemble human pancreatic cancer.
Their findings are published in Biomaterials. Prof Kano, who supervised
the study, explains, “No cancer is an island entire of itself. In
pancreatic cancer, fibrotic tissue often occupies much more space than
the cancer cells themselves. While numerous 3D models of pancreatic
cancer have been reported, ours is the first to allow the tuning of the
amount of fibrosis in the model.”
But, why does the presence of fibrosis hinder cancer treatment in the
first place Specifically, the dense and thick fibrotic tissue obstructs
the penetration of drugs into the tumor and limits anti-tumor immunity.
Assistant Professor Tanaka, who led the study, explains, “With the
5-year survival rate of pancreatic cancer at approximately 9% despite
decades of intensive research, a deeper understanding of the mechanisms
that underlie fibrosis in pancreatic cancer, as well as its
pathophysiological and therapeutic ramifications, is necessary.” Thus,
the scientists set out to find ways of understanding fibrotic mechanisms
in pancreatic cancer.
But, this was no easy task, as currently used experimental models of
pancreatic cancer, especially in vitro models, fail to replicate the
fibrotic components that are seen in pancreatic cancer. Thus, the
scientists reasoned that it was important to establish relevant
pancreatic cancer models that comprise not only cancer cells but also
cells involved in fibrosis. There were other challenges as well: an
analysis by the research team revealed that the area occupied by
fibrosis in human pancreatic cancer tissues ranges from 40 to 80% among
patients. Prof Kano says, “There was considerable heterogeneity among
patients, and for our 3D cell culture model to fully resemble human
pancreatic cancer, we wanted to make sure that we could recreate tissue
with any given amount of fibrosis.”
Fibrosis consists mainly of cells called “fibroblasts” and other
extracellular matrix components secreted by fibroblasts. Considering
this, the research team came up with a simple strategy: mix and culture
pancreatic cancer cells and fibroblasts at various ratios. “The strategy
seemed too simple to work,” Tanaka recollects with a laugh, “But much
to our pleasant surprise, it did!” The team successfully showed that by
varying the ratio of pancreatic cancer cells seeded against a fixed
number of fibroblasts, they could create pancreatic cancer tissues in
vitro with different amounts of fibrosis. Importantly, they showed that
the area occupied by fibrosis in these tissues can be experimentally
tuned to match the amount of fibrosis in the clinically observed range.
The team also went on to use the model to successfully understand the
molecular mechanisms by which a particular “phenotype” of fibroblasts,
characteristic to pancreatic cancer, occurs.
The scientists are optimistic that this novel model can complement other
well-established models of pancreatic cancer, especially with regard to
fibrosis. “The great thing about our model is that it is fairly simple
to create,” concluded Prof Kano. “We believe it will be useful in
mechanistic studies as well as in screening for drugs that target
fibrosis. This is just the beginning, but we hope to make a real
difference in the treatment of pancreatic cancer.”
Release URL: https://www.eurekalert.org/pub_releases/2020-07/ou-mam072220.php
Reference:
Title of original paper: Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements
Journal: Biomaterials
DOI: http://dx.doi.org/10.1016/j.biomaterials.2020.120077
Contact Person: Mitsunobu R. Kano
E-mail: mitkano(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
https://www.okayama-u.ac.jp/eng/research_highlights/index_id107.html
https://sdgs.okayama-u.ac.jp/en/
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