Establishment of a cell line from a Japanese patient useful for generating an in vivo model of malignant pleural mesothelioma

Our plain-English summary of Establishment of a cell line from a Japanese patient useful for generating an in vivo model of malignant pleural mesothelioma, by A. Sato, I. Torii, L.H. Tao, et al (Cancer Science, 2011).

The study

• Authors: A. Sato, I. Torii, L.H. Tao, M. Song, N. Kondo, Y. Yoshikawa, T. Hashimoto-Tamaoki, S. Hasegawa, T. Nakano, T. Tsujimura
• Journal: Cancer Science
• Published: 2011;102(3):648-55
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is a refractory tumor with increasing incidence. In the present study, we established six mesothelioma cell lines possessing two allele deletions of the p16(INK4A) gene and one allele deletion of the neurofibromatosis type 2 gene, MM16, MM21, MM26, MM35, MM46 and MM56, from pleural effusion fluids or surgically resected tumors of Japanese patients. MM21, MM26 and MM46 cells failed to develop tumors in BALB/c-nude mice following subcutaneous inoculation. MM16 and MM35 cells slowly generated tumors at the site of subcutaneous inoculation in BALB/c-nude mice, but lost the expression of mesothelioma-related markers such as calretinin, D2-40 and Wilms' tumor 1 in the subcutaneous tumors. On the other hand, MM56 cells rapidly generated tumors with the expression of calretinin and D2-40 in BALB/c-nude mice following subcutaneous inoculation. In addition, orthotopic implantation of MM56 cells into BALB/c-nude mice developed diffusely growing thoracic tumors by 3 weeks after implantation. Pleural effusions were observed in these mice 4 weeks after implantation. Thoracic tumors invaded aggressively into the chest wall 5 weeks after implantation and often metastasized into the lung, rib, peritoneum and pericardial cavity. On the pleural surface, MM56 cells were growing as single or multiple cell layers with the reactive mesothelium of recipient mice. These results indicate that MM56 cells can behave in a manner characteristic of human malignant pleural mesothelioma in the thoracic cavity of BALB/c-nude mice. The in vivo model using MM56 cells may be useful for studying the biological behavior of malignant pleural mesothelioma and developing its diagnostic and therapeutic strategies.

© 2011 Japanese Cancer Association.

In plain English

This laboratory study grew six mesothelioma cell lines (MM16, MM21, MM26, MM35, MM46 and MM56) from fluid around the lungs or from surgically removed tumors of six untreated Japanese patients with malignant pleural mesothelioma. The article's table marks all six patients as having asbestos exposure but gives no details of fibers or jobs. All six cell lines had lost both copies of the p16INK4A gene and one copy of the NF2 gene. When injected under the skin of nude mice, MM21, MM26 and MM46 cells formed no tumors. MM16 and MM56 cells formed tumors in all 12 mice, and MM35 cells in nine of 12. Only the MM56 tumors kept the mesothelioma markers calretinin and D2-40. When MM56 cells were placed in the chest cavity, chest tumors were found from 3 weeks and pleural fluid from 4 weeks. The tumors invaded the chest wall by 5 weeks and often spread to the lung, rib, peritoneum and pericardial cavity. The authors concluded that MM56 cells behave like human malignant pleural mesothelioma in these mice.

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: cell lines were established from patient samples, then implanted into mice (an animal experiment using human tumor cells)
• Who was studied: Six untreated Japanese patients with malignant pleural mesothelioma treated at the Hospital of Hyogo College of Medicine. Five were male and one female, aged 43 to 69 according to Table 1. Their cells were implanted into seven-week-old female BALB/c-nude mice. No dates are given.
• Exposure: Table 1 records asbestos exposure as positive for all six patients, with no fiber type, product, job or dose given. The experiments themselves did not involve asbestos: human mesothelioma cells were injected under the skin or into the chest cavity of mice.
• Main results:
  • All six cell lines had deletions of both copies (alleles) of the p16INK4A gene and of one copy of the NF2 gene.
  • After injection under the skin, MM21, MM26 and MM46 cells formed no tumors. MM16 and MM56 cells formed tumors in all 12 mice (24 sites), and MM35 cells in nine of 12 mice (18 of 24 sites).
  • Under the skin, MM56 tumors grew very aggressively, MM16 tumors moderately and MM35 tumors extremely slowly. Only the MM56 tumors kept the mesothelioma markers calretinin and D2-40.
  • In the chest cavity, MM16 cells formed nodules rather than diffuse tumors. MM35 cells formed no chest tumors within 6 weeks. Some MM35 mice became moribund with pleural effusions and chest tumors around 30 weeks after implantation.
  • Chest tumors were present in every MM56 mouse examined: 4 of 4 at 3 weeks, 4 of 4 at 4 weeks, 5 of 5 at 5 weeks, 5 of 5 at 6 weeks and 2 of 2 at 7 weeks. Pleural effusions were present in 0 of 4, 3 of 4, 3 of 5, 5 of 5 and 1 of 2 mice at the same times. Mice often became moribund around 7 weeks.
  • In MM56 mice, tumors invaded the chest wall by 5 weeks. Spread to the lung, rib, peritoneum and pericardial cavity was often seen over the 3 to 7 week experimental period.
  • On the pleural surface of MM56 mice, the human tumor cells stained positive for CD146, while the mouse's own reactive mesothelium stained negative. The two cell types were found side by side.
• The authors' conclusion: The authors concluded that MM56 cells reproduce the characteristic features of human malignant pleural mesothelioma in nude mice. They regarded the MM56 chest-cavity model as an animal model for studying the disease's behavior and for developing ways to diagnose and treat it.
• Limitations the authors state:
  • The authors stated that the MM35 cells were less useful because they produced tumors slowly. In the chest-cavity model, MM35 cells produced chest tumors in only two of five mice, 30 weeks after inoculation.
  • The authors noted that genetic abnormalities other than those in the p16INK4A and NF2 genes may explain why the six cell lines differed in forming tumors in mice.
  • For sarcomatoid mesothelioma, the authors considered it unlikely that how malignant the tumor is in humans matches whether it forms tumors in nude mice. The sarcomatoid line MM46 formed no tumors in mice.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Pleural Effusion, Calretinin, Podoplanin (D2-40), Peritoneum, Pericardial, Mesothelium.

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