Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: gene expression associated with metastatic potential in human lung cancer

Nakano,Tetsuhiro; Shimizu,Kimihiro; Kawashima,Osamu; Kamiyoshihara,Mitsuhiro; Kakegawa,Seiichi; Sugano,Masayuki; Ibe,Takashi; Nagashima,Toshiteru; Kaira,Kyoichi; Sunaga,Noriaki; Ohtaki,Youichi; Atsumi,Jun; Takeyoshi,Izumi

doi:10.3892/or.2012.1972

Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: gene expression associated with metastatic potential in human lung cancer

Authors:
- Tetsuhiro Nakano
- Kimihiro Shimizu
- Osamu Kawashima
- Mitsuhiro Kamiyoshihara
- Seiichi Kakegawa
- Masayuki Sugano
- Takashi Ibe
- Toshiteru Nagashima
- Kyoichi Kaira
- Noriaki Sunaga
- Youichi Ohtaki
- Jun Atsumi
- Izumi Takeyoshi
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Affiliations: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
Published online on: August 21, 2012 https://doi.org/10.3892/or.2012.1972
Pages: 1727-1735

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Abstract

Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.

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