BOCA RATON — Vijaya Iragavarpu-Charyulu, Ph.D., associate professor of Biomedical Science in the Charles E. Schmidt College of Medicine at Florida Atlantic University, received a $433,500 grant from the National Cancer Institute of the National Institutes of Health for a project titled “Role of CH13L in Accelerating Breast Cancer Metastasis: a Mechanistic Approach.”
Chitinase-3-like protein 1 or CH131L is a secreted glycoprotein in humans that is encoded by the CH13 L 1 gene and is implicated in inflammatory diseases such as asthma and cancer progression.
Iragavarapu-Charyulu and her Ph.D. student, Stephania Libreros, are focused on two specific aims in this project: To determine if inflammation associated with CH13L1 in the lung alters the pulmonary environment to attract circulating breast tumor cells and accelerates metastatic growth and to determine if inhibition of CH13L1 by either chitin microparticles, anti-CH13L1 neutralizing antibody or combination of these two decreases tumor metastasis.
The researchers hypothesize that CH13L1-induced pulmonary inflammation generates the proper environment for recruiting circulating breast cancer cells, thereby increasing the rate of metastasis to the lung. They anticipate that inhibiting CHI3L1 will reduce metastasis.
“Metastasis is responsible for a majority of breast cancer deaths,” said Iragavarapu-Charyulu. “Our studies show that the rate of recurrent metastasis of breast cancer is significantly higher if there is preexisting lung inflammation such as asthma.”
Asthma and pulmonary diseases are characterized by increased expression of CHI3L1. Rates of pulmonary inflammation due to pollution, allergies and smoking have been steadily increasing.
Iragavarapu-Charyulu’s research will provide a greater understanding of the role of CHI3L1 in enhancing metastasis and the tissue-specific molecular signals that act to exacerbate metastasis under conditions of chronic inflammation.
Moreover, limiting inflammation by use of molecules that block the activity of CHI3L1 in vivo has the potential to decrease metastasis for many cancer patients also suffering from inflammatory diseases. Combining immunotherapy (anti-CHI3L1 antibody) with the natural bio-product chitin particles could provide novel modes of treatment options for inhibiting metastatic diseases.
“We have recently shown that chitin microparticles, the biological binding partner for CHI3L1, decreases pulmonary metastasis and increases survival in mammary tumor-bearing mice,” said Iragavarapu-Charyulu. “It is our hope that through this research we can determine if changes in pulmonary tissue due to inflammation provide the necessary ‘soil’ for the circulating breast tumor cells.”
This project is supported by the National Cancer Institute and the National Center for Research Resources of the National Institutes of Health.