Hypoxia affects in vitro growth of newly established cell lines from patients with malignant pleural mesothelioma

Our plain-English summary of Hypoxia affects in vitro growth of newly established cell lines from patients with malignant pleural mesothelioma, by H. Goudarzi, Y. Hida, H. Takano, et al (Biomedical Research, 2013).

The study

• Authors: H. Goudarzi, Y. Hida, H. Takano, H. Teramae, H. Iizasa, J. Hamada
• Journal: Biomedical Research
• Published: 2013;34(1):13-21
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Human malignant pleural mesothelioma (MPM) is highly aggressive, and its prognosis is very poor. For an early diagnosis of MPM and developing new therapeutic strategies against the malignancy, it is necessary to better understand biological characteristics of MPM. In this study, we established two cell lines from pleural effusions derived from patients with MPM. Both cell lines expressed tumor markers of mesothelioma such as mesothelin, podoplanin, WT1, calretinin and keratin 5/6 whereas they did not express either CEA or TTF-1 which are often used as markers of lung adenocarcinoma. The cell lines harboured wild-type TP53, produced hyaluronic acid, and were not infected with SV40. When these two cell lines were cultured under hypoxia (1% O(2)), they showed particular responses to the hypoxic condition, distinct from those to normoxic condition (21% O(2)). Namely, the ability to form a colony originating from a single cell (plating efficiency and cloning efficiency) was stimulated under hypoxia in both cell lines. On the other hand, when the assays of cell growth were started at a relatively high cell density, the growth of both cell lines, regardless of anchorage-dependent or -independent, decreased under hypoxia. The differences of their growth between under hypoxia and under normoxia, and those depending on the cell density, may provide useful hints for developing a new strategy for diagnosis or therapy of MPM.

In plain English

This laboratory study examined cancer cells grown in dishes. The authors established two cell lines, HMM-1 and HMM-3, from fluid around the lungs (pleural effusions) of two men, aged 57 and 64, who had surgery for malignant pleural mesothelioma at Hokkaido University Hospital in 2006 and 2007. The article does not report the patients' asbestos exposure. Both cell lines carried mesothelioma markers and lacked the lung adenocarcinoma markers TTF-1 and CEA. They had wild-type TP53, did not express p16, and showed no evidence of SV40 virus infection. The authors compared growth in low oxygen (1%, called hypoxia) with normal air (21% oxygen). Under hypoxia, single cells formed more colonies in both lines. When many cells were seeded, growth fell under hypoxia. Six days after seeding 4,000 cells, HMM-1 cell numbers under hypoxia were about 65% of those under normal oxygen, and HMM-3 numbers were about 50%. Cell clusters (spheroids) grown under hypoxia were significantly smaller. The authors concluded that factors such as cell density change how these cells respond to hypoxia. They said they do not know whether this happens in other cell lines.

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) study: establishment and characterization of two new mesothelioma cell lines, and comparison of their growth under low versus normal oxygen
• Who was studied: Two cell lines (HMM-1 and HMM-3) grown from pleural effusions of two male patients, aged 57 and 64, who had surgery for malignant pleural mesothelioma at Hokkaido University Hospital in 2006 and 2007
• Exposure: Not asbestos: the cells were cultured under hypoxia (1% oxygen) compared with normoxia (21% oxygen). The article does not report the patients' asbestos exposure.
• Main results:
  • Both cell lines expressed mesothelioma markers (keratin 5/6, podoplanin, WT1, calretinin, mesothelin).
  • Neither cell line expressed TTF-1 or CEA, which are markers of lung adenocarcinoma.
  • Both cell lines had wild-type TP53 and did not express p16 protein.
  • Neither cell line showed evidence of SV40 infection.
  • In both cell lines, the ability of single cells to form colonies was enhanced under hypoxia.
  • Six days after seeding 4,000 cells, the HMM-1 cell number under hypoxia was approximately 65% of that under normoxia, and the HMM-3 cell number was approximately 50%.
  • Spheroids (cell clusters grown without attachment) formed under hypoxia were significantly smaller than those formed under normoxia (P less than 0.01).
  • Saturation density was lower in both cell lines under hypoxia than under normoxia.
  • HMM-1 cells grew much less than HMM-3 cells in all growth assays.
• The authors' conclusion: The authors concluded that their findings suggest a complex tumor environment in which factors such as cell density change how mesothelioma cells respond to hypoxia.
• Limitations the authors state:
  • The authors do not know whether the same growth responses occur in other mesothelioma cell lines or in other tumor cell lines.
  • Their explanation involving cancer stem cells is uncertain. Hypoxia may instead stimulate other cell populations.

Topics

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

Medical terms in this study, explained in our Lexicon: Hypoxia, Pleural Mesothelioma, Prognosis, Pleural Effusion, Tumor Marker, Mesothelioma, Mesothelin, Podoplanin (D2-40).

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