Critical role of defensins in respiratory viral infection induced breast cancer progression
Cancer Research Conference: American Association for Cancer Research Annual Meeting, ACCR
; 83(7 Supplement), 2023.
Article
in English
| EMBASE | ID: covidwho-20232118
ABSTRACT
Respiratory viral infections (RVI) such as influenza and COVID19 impact the host systemic immune system along with causing deleterious chronic inflammatory responses and respiratory distress. While the role of chronic inflammation in cancer is well-established, the role of RVI on tumorigenesis is poorly defined. To study the role of RVI on breast cancer, we first infected murine respiratory epithelial cells (mRES) with murine sendai virus (mSV), an analog for human parainfluenza virus. These infected mRES were co-cultured with 4T1 murine breast cancer cells in 11 dilution on a single 2D plate and also in trans-well format. Both in co-culture and transwell culture we saw a 40- 80% (p<0.05) increased proliferation of breast cancer cells. Similarly, when 4T1 cells were treated with the supernatant collected from infected mRES cells in 15 dilution, also demonstrated a 2.3 fold increased breast cancer cell proliferation. The cytokine analysis from the supernatant collected from infected mRES cells demonstrated a 17-23 fold enhanced secretion of alpha/beta-defensins. Direct treatment of alpha-defensin (cyptidin-4, 10 pg/mL) and beta-defensin-3 (mBD3, 20 pg/mL) on 4T1 cells demonstrated enhanced expression of chemokine metastatic receptor, CXCR4 (4.3 fold), angiogenic factor, VEGF (12.8 fold) and cell division favoring factor, CDK2 (8.1 fold). Further, analysis of infected mRES cells demonstrated upregulation of toll-like receptor 2 (TLR2) and NODlike receptor protein 3 (NLRP3) expression. Interesting, co-cultured of infected mRES with syngeneic murine CD4 T cells induced exhaustion phenotype (PD1+ and CTLA4+ ) differentiation of CD4 T cells. Taken together, these data suggest that respiratory viral infections through induction of cancer cell proliferation and inhibiting anti-tumor adaptive immune responses promote breast cancer proliferation.
4T1 cell line; adaptive immunity; airway epithelium cell; animal cell; animal experiment; breast cancer; cancer growth; cancer inhibition; CD4+ T lymphocyte; cell division; cell proliferation; chemotaxis assay kit; coculture; conference abstract; controlled study; dilution; exhaustion; female; gene expression; human; nonhuman; Paramyxovirinae; phenotype; protein expression; protein function; Sendai virus; supernatant; upregulation; viral respiratory tract infection; alpha defensin; angiogenic factor; beta defensin; beta defensin 3; chemokine; chemokine receptor CXCR4; cryopyrin; cyclin dependent kinase 2; cytokine; defensin; endogenous compound; receptor protein; toll like receptor 2; vasculotropin
Full text:
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Cancer Research Conference: American Association for Cancer Research Annual Meeting, ACCR
Year:
2023
Document Type:
Article
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