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The Role of Oncofetal Chondroitin Sulfate in the Tumor Microenvironment

Xu, Yiyi (2021) MOBN03 20202
Degree Projects in Molecular Biology
Popular Abstract
Oncofetal Chondroitin Sulfate, leave me alone, please.

Cancer, one of the most lethal diseases in the world, with a lack of efficient therapy for decades. Among the increasing research of potential therapeutic targets for cancers, oncofetal chondroitin sulfate (ofCS) came into our views. It is a special kind of chondroitin sulfate (CS), that is only expressed on the placenta and cancers and closely related to the development of cancers, including its formation, growth, and migration. Unfortunately, the functions and features of this ofCS remain unclear. Thus, an initial exploration to understand the ofCS was conducted in this study.

Given that pancreatic cancer is one of the most malignant cancers with a very low survival of... (More)
Oncofetal Chondroitin Sulfate, leave me alone, please.

Cancer, one of the most lethal diseases in the world, with a lack of efficient therapy for decades. Among the increasing research of potential therapeutic targets for cancers, oncofetal chondroitin sulfate (ofCS) came into our views. It is a special kind of chondroitin sulfate (CS), that is only expressed on the placenta and cancers and closely related to the development of cancers, including its formation, growth, and migration. Unfortunately, the functions and features of this ofCS remain unclear. Thus, an initial exploration to understand the ofCS was conducted in this study.

Given that pancreatic cancer is one of the most malignant cancers with a very low survival of patients, we planned to use pancreatic cancers as the research model here. The effects of two important features of tumors and their microenvironments (hypoxia and mutant p53 genes) on the expressions of ofCS were explored. A recombinant protein, rVAR2, was used as the specific binding reagents of ofCS here.

Firstly, ofCS is found to be positively expressed in two pancreatic cancer cell lines, iKras 4292 and iKras 9805. And it’s also been found that ofCS are secreted and deposited into the ECM, potentially by CAFs. Subsequently, the p53 genes in those iKras cells were temporarily knockdown with siRNA transfections and the ofCS expressions were compared. The binding of rVAR2 was largely induced in those p53 knockdown groups from iKras 9805 cells and cancer-associated fibroblasts (CAFs), indicating that p53 might influence the ofCS expressions from cancer cells and CAFs. Similarly, cells were cultured under hypoxic and normal conditions and then the comparison of rVAR2 bindings was studied. It was found that there’s no significant difference in the ofCS expressions between those groups.

In conclusion, PDAC cells and CAFs express ofCS. CAFs secrete and deposit ofCS into the extracellular matrix (ECM). And p53 might influence the ofCS expression from cancer cells and CAFs but more cell lines are needed for validations.

Master’s Degree Project in Molecular Biology 60 credits 2021
Department of Biology, Lund University

Advisor: Chris Madsen, Carmen Cupello-Rodriguez
Department of Laboratory Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Xu, Yiyi
supervisor
organization
course
MOBN03 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9068195
date added to LUP
2021-11-17 13:28:14
date last changed
2021-11-17 13:28:14
@misc{9068195,
  author       = {{Xu, Yiyi}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The Role of Oncofetal Chondroitin Sulfate in the Tumor Microenvironment}},
  year         = {{2021}},
}