TY - JOUR
T1 - Circulating tumor cells from a 4-dimensional lung cancer model are resistant to cisplatin
AU - Vishnoi, Monika
AU - Mishra, Dhruva K.
AU - Thrall, Michael J.
AU - Kurie, Jonathan M.
AU - Kim, Min P.
N1 - Funding Information:
M.P. Kim has received grant support from the Second John W. Kirklin Research Scholarship , the American Association for Thoracic Surgery Graham Research Foundation , and the Houston Methodist Foundation with a donation from J. Michael Jusbasche.
PY - 2014/9
Y1 - 2014/9
N2 - Objective To determine the effect of cisplatin on circulatory tumor cells (CTC) and tumor nodules in a four-dimensional (4D) lung cancer model. Methods CTCs from the 4D model seeded with H1299, A549, or H460 and respective cells that were grown under two-dimensional conditions in a Petri dish were treated with 50 μM cisplatin for 24 and 48 hours and cell viability was determined. The lung nodules in the 4D model were then treated with different continuous or intermittent doses of cisplatin and the nodule size, the number of CTCs, and the level of matrix metalloproteinase (MMP) were determined. Results Cisplatin led to a significant decrease in the viability of tumor cells grown under 2D conditions (P <.01) but not in CTCs from the 4D model after both 24 hours and 48 hours. Cisplatin led to regression of tumor nodules with both the continuous and intermittent treatments. Moreover, there was a significantly higher number of CTCs per tumor area (P <.05) and MMP-2 production per tumor area (P =.007) for all human lung cancer cell lines grown in the 4D model when treated with cisplatin. Conclusions The 4D lung cancer model allows for the isolation of CTCs that are resistant to cisplatin treatment. The model may allow us to better understand the biology of cisplatin resistance.
AB - Objective To determine the effect of cisplatin on circulatory tumor cells (CTC) and tumor nodules in a four-dimensional (4D) lung cancer model. Methods CTCs from the 4D model seeded with H1299, A549, or H460 and respective cells that were grown under two-dimensional conditions in a Petri dish were treated with 50 μM cisplatin for 24 and 48 hours and cell viability was determined. The lung nodules in the 4D model were then treated with different continuous or intermittent doses of cisplatin and the nodule size, the number of CTCs, and the level of matrix metalloproteinase (MMP) were determined. Results Cisplatin led to a significant decrease in the viability of tumor cells grown under 2D conditions (P <.01) but not in CTCs from the 4D model after both 24 hours and 48 hours. Cisplatin led to regression of tumor nodules with both the continuous and intermittent treatments. Moreover, there was a significantly higher number of CTCs per tumor area (P <.05) and MMP-2 production per tumor area (P =.007) for all human lung cancer cell lines grown in the 4D model when treated with cisplatin. Conclusions The 4D lung cancer model allows for the isolation of CTCs that are resistant to cisplatin treatment. The model may allow us to better understand the biology of cisplatin resistance.
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U2 - 10.1016/j.jtcvs.2014.05.059
DO - 10.1016/j.jtcvs.2014.05.059
M3 - Article
C2 - 25129597
AN - SCOPUS:84908518413
SN - 0022-5223
VL - 148
SP - 1056
EP - 1064
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 3
ER -