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Start Over Topic adaptation Publication Year Range Last 10 years Publisher springer netherlands
595 results

3. Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis

Author

Yasumasa Kato, Shusaku Sutoo, Atsuko Suzuki, and Toyonobu Maeda

Subjects
0301 basic medicine, Male, Cancer Research, medicine.medical_specialty, Acidic extracellular pH, Matrix metalloproteinase, Metastasis, 03 medical and health sciences, Carcinoma, Lewis Lung, Mice, 0302 clinical medicine, Serial passage, Internal medicine, Cell Line, Tumor, Extracellular, medicine, Tumor Microenvironment, Animals, Neoplasm Invasiveness, Adaptation, Neoplasm Metastasis, Lung, Hematology, Chemistry, Lewis lung carcinoma, General Medicine, Hydrogen-Ion Concentration, medicine.disease, Primary tumor, Matrix Metalloproteinases, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, MMP-9, Extracellular Space, LLC, Research Paper
Abstract

Acidic extracellular pH (pHe) is an important microenvironment for cancer cells. This study assessed whether adaptation to acidic pHe enhances the metastatic phenotype of tumor cells. The low metastatic variant of Lewis lung carcinoma (LLCm1) cells were subjected to stepwise acidification, establishing acidic pHe-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 α-smooth muscle actin expression was reduced. Despite serial passage of these cells at pH 7.4, high invasive activity through Matrigel® was sustained for at least 28 generations. Thus, adaptation to acidic pHe 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. Electronic supplementary material The online version of this article (10.1007/s10585-019-09990-1) contains supplementary material, which is available to authorized users.

Published
2019