Monocarboxylate transporters 1 and 4 are involved in the invasion activity of human lung cancer cells

• Published in: Cancer science Vol. 102; no. 5; pp. 1007 - 1013
• Main Authors: Izumi, Hiroto, Takahashi, Mayu, Uramoto, Hidetaka, Nakayama, Yoshifumi, Oyama, Tsunehiro, Wang, Ke‐Yong, Sasaguri, Yasuyuki, Nishizawa, Shigeru, Kohno, Kimitoshi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2011; Blackwell
• Subjects: Basigin - metabolism; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cell Movement - physiology; Gene Knockdown Techniques; Humans; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; Monocarboxylic Acid Transporters - metabolism; Muscle Proteins - metabolism; Neoplasm Invasiveness; Pneumology; RNA, Small Interfering; Symporters - metabolism; Tumors; Tumors of the respiratory system and mediastinum; Human; Lung disease; Cancerology; Respiratory disease; Lung cancer; Bronchus disease; Malignant tumor; Metastasis; Biological activity; Tumor cell; Invasion; Cancer
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2011.01908.x

Cancer cells show constitutive upregulation of glycolysis, and the concentration of lactate thus produced correlates with prognosis. Here, we examined whether lactate concentration and lactate transporter expression are related to migration and invasion activity. We found that the expression of the monocarboxylate transporters MCT1 and MCT4, but not MCT5, in human lung cancer cell lines was significantly correlated with invasiveness. To clarify the effects of MCT1 and MCT4 expression on invasion, we performed migration and invasion assays after transfection with siRNA specific for MCT1 or MCT4. Knockdown of MCT1 or MCT4 did not influence cell migration but reduced invasion; this was also observed for knockdown of the lactate transporter‐associated protein basigin. We also demonstrated that both expression and activity of MMP9 and MMP2 were not correlated with invasion activity and not regulated by MCT1, MCT4 and basigin. Furthermore, the addition of lactate did not increase migration and invasion activity, but low concentration of 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS), a general anion channel blocker, as well as other MCT inhibitors quercetin and simvastatin, inhibited cell invasion without influencing migration activity and the cellular expression of MCT1 and MCT4. This is the first report suggesting that lactate transporters are involved in human cancer cell invasiveness. As such, these proteins may be promising targets for the prevention of cancer invasion and metastasis. (Cancer Sci 2011; 102: 1007–1013)