Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage MutantK-ras Lung Cancer
Technical Report,15 Sep 2014,14 Sep 2015
UNIVERSITY OF TEXAS SOUTHWESTERN Dallas United States
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The overall goal of this proposal is to understand the role of the Hh pathway in the maintenance and proliferation of lungadenocarcinoma progenitor cells and to establish therapeutic strategies that target the stem cell and its microenvironment forearly stage lung cancer. Toward this end, we successfully labeled AlexaFluor 647 to anti-SHHIHH antibody 5E1 andsuccessfully FACS-sorted SHH and SHH- cells from high SHH-expressing lung cancer cell lines. The SHH cell populationhad increased SHH mRNA expression versus SHH- cell population although SHH- cells also expressed some increased SHHexpression compared to normal HBEC7kt lung epithelia. Surprisingly, in liquid colony formation and tissue culturedproliferation assays, SHH- cells formed more colonies and proliferated faster than SHH cells. Further refinement of potentiallung cancer stem cells will be performed using a combination of SHHALDHNOTCH3 as potential stem cell markers. We willalso test the hypothesis that SHH cell population may be a quiescent stem cell population and SHH- cells are transientamplifying cells. We have also established an orthotopic xenograft metastatic lung cancer model with HCC515 cells thatexpress high levels of SHH. We will use this model for future studies for the prevention of cancer metastasis.