Autocrine CXCL13-CXCR5 signaling potently induces EMT of breast cancer cells via RANKL-Src-PI3Kp110α  during lymph node metastasis — ASN Events
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  3. Autocrine CXCL13-CXCR5 signaling potently induces EMT of breast cancer cells via RANKL-Src-PI3Kp110α  during lymph node metastasis

Autocrine CXCL13-CXCR5 signaling potently induces EMT of breast cancer cells via RANKL-Src-PI3Kp110α  during lymph node metastasis (#222)

Subir Biswas 1 , Arnab Gupta 2 , Dmitry V Kuprash 3 , Arindam Bhattacharyya 1
  1. Immunology Lab, Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
  2. Department of Surgical Oncology, Saroj Gupta Cancer Centre and Research Institute, Kolkata, West Bengal, India
  3. Laboratory of Immunoregulation, Engelhardt Institute of Molecular Biology, Moscow, Russia

Background

Epithelial to mesenchymal transition (EMT) is an important hallmark of metastasis. Increased EMT is associated with lymph node metastasis (LNM). We investigated EMT inducing potential of chemokine CXCL13 in breast cancer (BC) cell lines and CXCL13-CXCR5 signaling in primary breast tumors in association with different epithelial and mesenchymal markers and EMT inducers.

Methods

Chemokine CXCL13 and and its sole receptor CXCR5 were evaluated in 98 primary breast tumor samples from breast cancer patients with infiltrating duct carcinoma (IDC). BC cell lines were transduced with CXCR5, treated with recombinant CXCL13 and assessed for cell migration, EMT markers and activation of intracellular signaling pathways.

Results

A total of 56 patients were LNM positive and 42 were LNM negative. LNM positivity was positively associated with co-expression of CXCL13 and CXCR5. Increased expression of various mesenchymal molecular markers and regulators and decreased expression of epithelial marker E-cadherin was found in CXCL13-stimulated BC cells and tumors from CXCL13-CXCR5 co-expressing patients. Experiments with protein kinase inhibitors demonstrated that CXCL13 stimulates EMT and expression of matrix metalloproteinase (MMP9) via RANKL-Src axis.

Conclusion

This study demonstrated the prognostic value of CXCL13-CXCR5 co-expression in primary BC. Moreover, it showed the EMT inducing potential of CXCL13. RANKL-Src axis may present a therapeutic target in LNM positive BC patients.