Bex1 significantly contributes to the proliferation and invasiveness of malignant tumor cells

Our plain-English summary of Bex1 significantly contributes to the proliferation and invasiveness of malignant tumor cells, by T. Doi, H. Ogawa, Y. Tanaka, et al (Oncology Letters, 2020).

The study

• Authors: T. Doi, H. Ogawa, Y. Tanaka, Y. Hayashi, Y. Maniwa
• Journal: Oncology Letters
• Published: 2020;20(6):362
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Invasion has a significant role in cancer progression, including expansion to surrounding tissue and metastasis. Previously, we assessed the invasive ability of cancer cells using an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) method by which cancer cell invasion can be easily visualized. The present study examined multiple lung adenocarcinoma and malignant pleural mesothelioma (MPM) cell lines using the DL-CGH method and identified inherently invasive cell lines. Next, by comparing gene expression between invasive and non-invasive cells by cDNA microarray, the potential candidate gene brain-expressed x-linked protein 1 (Bex1) was identified to be involved in cancer invasion, as it was highly expressed in the invasive cell lines. Downregulation of Bex1 suppressed the invasion and proliferation of the invasive tumor cell lines. The findings of the present study suggested that Bex1 may promote metastasis in vivo and could be a potential oncogene and molecular therapeutic target in lung adenocarcinoma and MPM.

Copyright: © Doi et al.

In plain English

This was a laboratory study of human cancer cells grown in dishes, not of people or animals. The authors tested four cell lines: two lung adenocarcinoma lines (A549 and A110L) and two malignant pleural mesothelioma lines (NCI-H28 and MSTO-211H). They used a collagen gel method they had developed earlier to see whether cells spread into a surrounding gel layer. A110L and MSTO-211H cells invaded strongly, while A549 and NCI-H28 cells showed almost no invasion. Comparing gene activity, a gene called Bex1 was much more active in the invasive lines: 2,354 times higher in A110L than in A549, and 3,951 times higher in MSTO-211H than in NCI-H28. When the authors reduced Bex1 in the two invasive lines, those cells showed almost no invasion, fewer living cells in the gel, and significantly reduced growth. The authors concluded that Bex1 is a candidate cancer-promoting gene in lung adenocarcinoma and pleural mesothelioma and may be a treatment target. They said their main purpose was to report this candidate gene urgently, and that they were planning a future in vivo study and a study using clinical samples. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-line experiment: invasion assay in collagen gel, gene expression microarray comparison, and gene knockdown (RNA interference) of Bex1
• Who was studied: Four commercially obtained human cancer cell lines: lung adenocarcinoma lines A549 and A110L (from the Riken Bioresource Center) and malignant pleural mesothelioma lines NCI-H28 and MSTO-211H (from the American Type Culture Collection). No human participants.
• Exposure: No asbestos exposure was studied. The experimental manipulation was reducing (knocking down) Bex1 gene expression with small interfering RNA (siRNA), compared with untreated cells, cells treated with the transfection reagent only, and cells given a non-silencing control siRNA.
• Main results:
  • In the collagen gel assay, A549 (lung adenocarcinoma) and NCI-H28 (mesothelioma) cells showed almost no invasion into the outer layer, while A110L (lung adenocarcinoma) and MSTO-211H (mesothelioma) cells showed strong invasion.
  • On the microarray, Bex1 expression was 2,354 times higher in invasive A110L than in non-invasive A549 lung adenocarcinoma cells, and 3,951 times higher in invasive MSTO-211H than in non-invasive NCI-H28 mesothelioma cells.
  • RT-PCR also showed higher Bex1 expression in A110L and MSTO-211H cells than in A549 and NCI-H28 cells.
  • After Bex1 was knocked down, A110L and MSTO-211H cells showed almost no invasion into the outer gel layer.
  • In A110L cells at day 14, the stained living-cell area (pixel count) was 181,748 in untreated cells, 184,928 with reagent only, 191,934 with control siRNA, and 95,914 with Bex1 siRNA, which the authors reported as significantly decreased.
  • In MSTO-211H cells at day 10, the stained living-cell area (pixel count) was 220,502 in untreated cells, 236,713 with reagent only, 205,433 with control siRNA, and 128,262 with Bex1 siRNA, also reported as significantly decreased.
  • With Bex1 knocked down, A110L and MSTO-211H cells showed significantly reduced cell proliferation (n=5 samples per group).
  • The authors interpreted the growth results as indicating that Bex1 may act more on cell proliferation than on cell death.
• The authors' conclusion: The authors concluded that overexpression of Bex1 promotes tumor proliferation and invasion, identifying Bex1 as a candidate oncogene in lung adenocarcinoma and malignant pleural mesothelioma, and that Bex1 may be a molecular treatment target.
• Limitations the authors state:
  • The authors said the main purpose of the study was to report a candidate gene urgently, and that an assessment of Bex1 overexpression in non-invasive cells through an in vivo study, and a study using clinical samples, were planned for the future.

Topics

Medical terms in this study, explained in our Lexicon: Metastasis, Collagen, Lung Adenocarcinoma, Pleural Mesothelioma.

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