2020年2月
Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis
CLINICAL & EXPERIMENTAL METASTASIS
- ,
- ,
- ,
- 巻
- 37
- 号
- 1
- 開始ページ
- 133
- 終了ページ
- 144
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s10585-019-09990-1
- 出版者・発行元
- SPRINGER
Acidic extracellular pH (pH(e)) is an important microenvironment for cancer cells. This study assessed whether adaptation to acidic pH(e) enhances the metastatic phenotype of tumor cells. The low metastatic variant of Lewis lung carcinoma (LLCm1) cells were subjected to stepwise acidification, establishing acidic pH(e)-adapted (LLCm1A) cells growing exponentially at pH 6.2. These LLCm1A cells showed increased production of matrix metalloproteinases (MMPs), including MMP-2, -3, -9, and -13, and pulmonary metastasis following injection into mouse tail veins. Although LLCm1A cells exhibited a fibroblastic shape, keratin-5 expression was increased and alpha-smooth muscle actin expression was reduced. Despite serial passage of these cells at pH 7.4, high invasive activity through Matrigel (R) was sustained for at least 28 generations. Thus, adaptation to acidic pH(e) resulted in a more invasive phenotype, which was sustained during passage at pH 7.4, suggesting that an acidic microenvironment at the primary tumor site is important in the acquisition of a metastatic phenotype.
- リンク情報
- ID情報
-
- DOI : 10.1007/s10585-019-09990-1
- ISSN : 0262-0898
- eISSN : 1573-7276
- PubMed ID : 31489536
- Web of Science ID : WOS:000511790500013