Author of

• 18272

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  P3.01 - Poster Session with Presenters Present (ID 469)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18317

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    P3.01-045 - Sex Differences in CXCR4-Dependent Motility of NSCLC Cells (ID 4932)

    14:30 - 14:30  |  Author(s): Y. Wu
    • Abstract

    Background:
    The overwhelming majority of deaths due to lung cancer result from metastatic progression of the disease. Cytokines, a group of proteins involved in cell signaling, play an important role in activating the migratory and invasive capabilities of cancer cells, and studies have implicated the stromal-derived factor 1 (SDF-1/CXCL12)-CXCR4 cytokine signaling axis in the progression of several metastatic cancers, including that of the lung. Our previous investigations have shown that survival outcomes of female stage IV non-small cell lung cancer (NSCLC) patients with high CXCR4 levels are significantly worse compared to those of patients with low CXCR4, whereas male patients show no difference in survival. Studies in NSCLC cell lines have observed a link between CXCR4/SDF-1 and estrogen receptor (ER) function, as well as proliferation in response to treatment with estradiol (an estrogen) specifically in female cell lines. These previous results form the rationale for this project, which explores potential sex differences in the motility of NSCLC cell lines in response to cytokine and estrogen stimulation.
    
    Methods:
    Western blotting and PCR methodologies were used to assess the downstream activation of CXCR4 and estrogen receptor signaling as a means to confirm their activity in the cell lines studied. The migratory potential of NSCLC cells was measured using wound healing migration assays (scratch tests). Cells were incubated in phenol red-free RPMI 1640 media with or without the reagents of interest (SDF-1, beta-estradiol, estrogen and CXCR4 antagonists, among others) and the migration of cells into the wound was quantified to approximate the metastatic behavior of NSCLC cells in the presence or absence of the aforementioned stimuli.
    
    Results:
    All NSCLC cells studied showed high levels of CXCR4, but ER expression varied within our cell line panel, largely by gender of origin. Our preliminary data show a tentative but observable difference in how male and female NSCLC cells respond to both stimulation and inhibition of the CXCR4 axis. In addition, estrogen and SDF-1 co-stimulation induces a greater increase in cell motility of female NSCLC cells.
    
    Conclusion:
    The results observed may suggest a possible mechanism, through interactions between CXCR4 and estrogen receptor signalling pathways, to explain the extreme survival differences between male and female stage IV NSCLC patients with high CXCR4 expression.