Open Access

Intratumoral heterogeneity of glutaminase and lactate dehydrogenase A protein expression in colorectal cancer

  • Authors:
    • Yuta Mizuno
    • Kimiaki Hattori
    • Kohei Taniguchi
    • Keitaro Tanaka
    • Kazuhisa Uchiyama
    • Yoshinobu Hirose
  • View Affiliations

  • Published online on: February 13, 2020     https://doi.org/10.3892/ol.2020.11390
  • Copyright: © Mizuno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The high expression of metabolic enzymes, including glutaminase (GA) and lactate dehydrogenase A (LDHA), which contribute to bioenergetics and biosynthesis of mammalian cells, has been identified in a variety of cancer types. The current study indicated intratumoral heterogeneity with respect to protein expression of the metabolic enzymes in colorectal cancer (CRC). GA protein expression was determined using immunohistochemistry in 98 cases of surgically resected T3 CRC. A total of 75 cases (74%) exhibited moderate to strong immunopositivity of GA based on whole‑section examination. A significant correlation was demonstrated between GA expression and clinicopathological features, including histological type and tumor budding in a patient population. Detailed histological analysis revealed the upregulation of GA protein expression at the invasive margin, including tumor budding of CRC tissues. Semi‑quantitative examination revealed a significant difference in immunoexpression level of GA between the invasive margin and central CRC. However, LDHA expression exhibited an opposite pattern, with expression elevated at the center and significantly decreased at the tumors invasive margin. Immunohistochemical expression of another glycolytic enzyme hexokinase II was equivalent in both regions. Furthermore, gene silencing of GLS1, which encodes GA protein, and GA inhibitor treatment significantly inhibited cell growth of CRC cell lines. Therefore, the results of the present study demonstrated that the alteration in GA and LDHA expression is more prominent at the invasive margin, which involves tumor budding in CRC.

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APA
Mizuno, Y., Hattori, K., Taniguchi, K., Tanaka, K., Uchiyama, K., & Hirose, Y. (1899). Intratumoral heterogeneity of glutaminase and lactate dehydrogenase A protein expression in colorectal cancer. Oncology Letters, 0, 0-0. https://doi.org/10.3892/ol.2020.11390
MLA
Mizuno, Y., Hattori, K., Taniguchi, K., Tanaka, K., Uchiyama, K., Hirose, Y."Intratumoral heterogeneity of glutaminase and lactate dehydrogenase A protein expression in colorectal cancer". Oncology Letters 0.0 (1899): 0-0.
Chicago
Mizuno, Y., Hattori, K., Taniguchi, K., Tanaka, K., Uchiyama, K., Hirose, Y."Intratumoral heterogeneity of glutaminase and lactate dehydrogenase A protein expression in colorectal cancer". Oncology Letters 0, no. 0 (1899): 0-0. https://doi.org/10.3892/ol.2020.11390