Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells

Our plain-English summary of Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells, by T. Saji, M. Nishita, H. Ogawa, et al (Genes to Cells, 2018).

The study

• Authors: T. Saji, M. Nishita, H. Ogawa, T. Doi, Y. Sakai, Y. Maniwa, Y. Minami
• Journal: Genes to Cells
• Published: 2018;23(7):606-613
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis and closely related to exposure to asbestos. MPM is a heterogeneous tumor with three main histological subtypes, epithelioid, sarcomatoid, and biphasic types, among which sarcomatoid type shows the poorest prognosis. The Ror-family of receptor tyrosine kinases, Ror1 and Ror2, is expressed in various types of tumor cells at higher levels and affects their aggressiveness. However, it is currently unknown whether they are expressed in and involved in aggressiveness of MPM. Here, we show that Ror1 and Ror2 are expressed in clinical specimens and cell lines of MPM with different histological features. Studies using MPM cell lines indicate that expression of Ror2 is associated tightly with high invasiveness of MPM cells, whereas Ror1 can contribute to their invasion in the absence of Ror2. However, both Ror1 and Ror2 promote proliferation of MPM cells. We also show that promoted invasion and proliferation of MPM cells by Ror signaling can be mediated by the Rho-family of small GTPases, Rac1, and Cdc42. These findings elucidate the critical role of Ror signaling in promoting invasion and proliferation of MPM cells.

© 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

In plain English

This was a laboratory study of two proteins called Ror1 and Ror2 in malignant pleural mesothelioma. It did not measure asbestos exposure. The authors stained tumor tissue removed from 5 patients at Kobe University Hospital, Japan. Tumor cells were positive for both proteins in all 5 specimens, which included epithelioid and sarcomatoid tumors. Neither protein was detected in normal lung tissue. Ror2 was also clearly detected, and Ror1 marginally, in noninvasive, abnormal mesothelial cells within the specimens. The authors then tested three mesothelioma cell lines grown in the lab. The sarcomatoid line H2052 had the most Ror2 and was the most invasive. Lowering Ror2 significantly reduced invasion in the two lines that made Ror2 (H2452 and H2052). Lowering Ror1 reduced invasion only in H28, the line lacking Ror2. Lowering Ror1 reduced cell growth in all three lines, and lowering Ror2 reduced growth in H2452 and H2052. In two lines, the proteins Rac1 and Cdc42 appeared to carry these signals. The authors concluded that Ror1 and Ror2 might be possible diagnostic or treatment targets, and said larger studies are needed.

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 study (brief report). It combined staining of surgical tumor specimens with experiments on human mesothelioma cell lines grown in culture, in which specific genes were switched down using siRNA.
• Who was studied: Resected malignant pleural mesothelioma tissue from 5 patients at Kobe University Hospital, Japan, plus three human mesothelioma cell lines: H28 (epithelioid), H2452 (biphasic) and H2052 (sarcomatoid).
• Exposure: No asbestos exposure was studied. Asbestos is mentioned only as background. The study examined the Ror1 and Ror2 proteins and the effect of reducing them in mesothelioma cells.
• Main results:
  • Tumor cells in all 5 patient specimens were positive for Ror1 and Ror2. Neither protein was detected in normal lung tissue next to the tumors.
  • Ror2 was detected at apparent levels, and Ror1 at marginal levels, in noninvasive, dysplastic pleural mesothelial cells within the specimens. The authors suggested this was probably associated with asbestos-induced chronic inflammation, but they did not test this.
  • Among the cell lines, Ror2 was most prominent in H2052, also detected in H2452, and almost undetectable in H28.
  • H2052 cells, which expressed the most Ror2, were the most invasive of the three cell lines.
  • Reducing Ror2 significantly inhibited invasion of H2452 and H2052 cells. It did not affect H28 cells.
  • Reducing Ror1 significantly inhibited invasion of H28 cells, but not of H2452 or H2052 cells.
  • Reducing Ror1 significantly reduced proliferation in all three cell lines. Reducing Ror2 significantly reduced proliferation of H2452 and H2052 cells.
  • Reducing Rac1 or Cdc42 significantly inhibited invasion and proliferation of H28 and H2452 cells.
• The authors' conclusion: The authors concluded that Ror1 and/or Ror2 are expressed highly in mesothelioma tissues and cell lines and promote invasion and proliferation, partly through Rac1 and Cdc42. They suggested these molecules might be novel diagnostic and/or therapeutic targets for MPM.
• Limitations the authors state:
  • Only 5 patient specimens were examined. The authors said larger numbers are needed to relate Ror1 and Ror2 to clinical and tissue features.
  • How Ror1 and Ror2 become expressed in mesothelioma cells, and how their signaling works, remains to be clarified.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Histological Subtype, Epithelioid, Sarcomatoid, Biphasic Mesothelioma.

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