Leukotrienes Mediated Neutrophils-promoted Xenograft Formation
Refereed conference paper presented and published in conference proceedings


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AbstractExpression of the GRO CXC chemokines (CXCL1-3) are commonly found in various cancer cells. However, their roles in promoting cancer formation are largely unknown. Previously, using stable clones of GPCR MAS-overexpressing CHO cells, our lab has established a GRCP MAS-driven, copy number variation-mediated ovarian xenograft model that expressed highly CXCL1 and CXCL3 [Int J Cancer 125: 1316-1327 (2009)]. Immunohistochemical and qPCR studies of the xenografts indicated that leukotriene A4 hydrolase (LTA4H) was constitutively expressed in both the tumorigenic stable MAS-overexpressing CHO cell clone Mc0M80 and the stromal cells of xenografts. In addition, leukotriene BLT1 receptors were detected abundantly in xenografts and neutrophils. The results suggested an active leukotriene signaling network within the ovarian xenografts. In vitro cell studies indicated that leukotrienes did not exert any growth-enhancing effects on the Mc0M80 cells or cancer-associated fibroblasts (CAF). By contrast, leukotriene LTB4, but not LTD4, promoted cell growth and triggered a chemotactic response on neutrophils. Of interest, co-cultures of the tumorigenic Mc0M80 cells with neutrophils, but not with CAF, promoted cell growth of Mc0M80 cells. Furthermore, high expression of CXCR2, receptors for GRO chemokines, was detected in neutrophils, but not in cancer cells and CAF. These results suggest cancer cell-derived GRO chemokines induced neutrophils infiltration into xenografts, which in turn established a leukotriene signaling microenvironment that enhanced neutrophils recruitment and promoted cancer cell growth, resulting in xenograft formation. Consistent with the hypothesis, co-injection of Mc0M80 cells and neutrophils tended to speed up xenograft formation, and growth of xenografts was significantly suppressed by 5-lipoxygenase (5-LOX) inhibitor zileuton. Our work suggests leukotriene signaling pathway and neutrophils could be novel targets for GRO-overexpressing cancers.
All Author(s) ListKa-Long CHU, Chun CHU, Susanna S LEE, Helen WISE, Wing-Tai CHEUNG
Name of Conference2017 Cold Spring Harbor Asia Conference
Start Date of Conference22/10/2017
End Date of Conference26/10/2017
Place of ConferenceJiangsu
Country/Region of ConferenceChina
Year2017
Month10
Day22
LanguagesEnglish-United States

Last updated on 2018-31-05 at 12:55