Title:The Potential Role of Claudins in Regulation of Metastasis and Development of Drug Resistance in Breast Cancer
Volume: 7
Author(s): Hemantkumar Patadia, Ankita Priyadarshini, Jay Ranade and Ajit Gangawane*
Affiliation:
- Department of Paramedical and Health Sciences, Faculty of Medicine, Parul University, Vadodara, Gujarat,India
Keywords:
Leukocyte transendothelial migration, breast cancer, claudins, chemotherapy resistance, cancer resistance, metastasis.
Abstract:
Background: Breast Cancer is a recurrent problem across the world. According to a report,
breast cancer has the second highest mortality rate in women globally. Despite having an advanced
degree of chemotherapy, resistance is developed against the therapies. Studies showed that anthracyclins
like doxorubicin used in the treatment of breast cancer are found to develop resistance, which is
not easy to identify. Mutations in the tumor suppressor gene P53 are associated with the primary resistance
to doxorubicin and thus inducing an early relapse of breast tumors. Resistance against
Doxorubicin is not identifiable easily. Development of resistance and metastasis of tumors are the two
processes that cannot be separated from each other. It is widely known that endothelium has a major
role in controlling metastasis and tumor cell invasion. Endothelial cells express different adhesion
molecules during recruitment of leukocytes in localized area, which is called leukocyte extravasation
or diapedesis, or leukocyte trans endothelial migration (LEM). LEM (leukocyte trans endothelial migration)
plays crucial role in the inflammation of breast cancer tissues.
Objective: Predicting the role of deregulation of claudins in leukocyte trans endothelial migration in
breast cancer metastasis and resistance.
Methods: The breast cancer proteomic metadata was collected and compared among the common candidates.
The enrichment analysis of those common candidates was performed using a network analyst.
Results: The analysis of breast cancer genes obtained from dbDEPC showed probable involvement of
4 candidate genes belonging to the claudin family. Claudins are responsible for the migration of an
increased amount of leukocytes in the breast tumor region, which increases the inflammation and may
contribute to worsening the disease progression.
Conclusion: We believe these candidates also contribute in the development of resistance to chemotherapy.