CD146 and insulin-like growth factor 2 mRNA-binding protein 3 predict prognosis of asbestos-induced rat mesothelioma

Our plain-English summary of CD146 and insulin-like growth factor 2 mRNA-binding protein 3 predict prognosis of asbestos-induced rat mesothelioma, by Y. Okazaki, H. Nagai, S.H. Chew, et al (Cancer Science, 2013).

The study

• Authors: Y. Okazaki, H. Nagai, S.H. Chew, J. Li, S. Funahashi, T. Tsujimura, S. Toyokuni
• Journal: Cancer Science
• Published: 2013;104(8):989-95
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM), which is associated with asbestos exposure, is one of the most deadly tumors in humans. Early MM is concealed in the serosal cavities and lacks specific clinical symptoms. For better treatment, early detection and prognostic markers are necessary. Recently, CD146 and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) were reported as possible positive markers of MM to distinguish from reactive mesothelia in humans. However, their application on MM of different species and its impact on survival remain to be elucidated. To disclose the utility of these molecules as early detection and prognostic markers of MM, we injected chrysotile or crocidolite intraperitoneally to rats, thus obtaining 26 peritoneal MM and establishing 11 cell lines. We immunostained CD146 and IMP3 using paraffin-embedded tissues and cell blocks and found CD146 and IMP3 expression in 58% (15/26) and 65% (17/26) of MM, respectively, but not in reactive mesothelia. There was no significant difference in both immunostainings for overexpression among the three histological subtypes of MM and the expression of CD146 and IMP3 was proportionally associated. Furthermore, the overexpression of CD146 and/or IMP3 was proportionally correlated with shortened survival. These results suggest that CD146 and IMP3 are useful diagnostic and prognostic markers of MM.

© 2013 Japanese Cancer Association.

In plain English

This was an animal experiment in rats. The authors injected F1 hybrid rats (Fischer344 crossed with Brown-Norway) twice into the abdomen with chrysotile or crocidolite asbestos at 6 and 7 weeks of age and observed them for up to 600 days, with earlier euthanasia for abdominal swelling or marked weight loss. They studied 26 rats (15 males, 11 females) with peritoneal malignant mesothelioma: 4 epithelioid, 9 biphasic and 13 sarcomatoid. Tumors were stained for the proteins CD146 and IMP3, and cell lines were tested by western blot. CD146 was found in 15 of 26 tumors (58%) and IMP3 in 17 of 26 (65%), and the two were significantly associated (P = 0.018). Rats whose tumors showed high levels (2+ or 3+) of CD146, or of IMP3, had shorter survival than rats with lower levels (P less than 0.05). Rats high for both had shorter survival than rats low for both (P less than 0.01). Three other markers (HIF-1a, cyclin D1, Ki-67) showed no significant survival difference. The authors concluded that CD146 and IMP3 are good diagnostic and prognostic markers in mesothelioma.

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: Animal experiment (asbestos-induced mesothelioma in rats), with immunohistochemistry, western blot of cell lines, and Kaplan-Meier survival analysis with log-rank tests
• Who was studied: 26 F1 hybrid rats (female Fischer344 crossed with male Brown-Norway; 15 males and 11 females), bred at Nagoya University, Japan, that developed peritoneal malignant mesothelioma (4 epithelioid, 9 biphasic, 13 sarcomatoid). Mesothelioma cell lines were also studied, some of them established in a previous project.
• Exposure: Two intraperitoneal injections of 1 mL of asbestos fiber at 5 mg per mL (chrysotile or crocidolite, Union for International Cancer Control grade) at 6 and 7 weeks of age. The rats were observed for up to 600 days and were killed earlier if they developed abdominal distention from ascites or marked weight loss. Some cell lines came from rats given amosite.
• Main results:
  • CD146 staining was positive in all 4 epithelioid tumors, 4 of 9 biphasic and 7 of 13 sarcomatoid tumors
  • Overall, 58% (15 of 26) of the rat mesotheliomas were CD146-positive
  • 65% (17 of 26) of the rat mesotheliomas were IMP3-positive
  • CD146 and IMP3 protein levels in the tumors were significantly associated (Fisher's exact test, P = 0.018)
  • Rats with CD146 overexpression (2+ or 3+) had shorter survival than rats with CD146 1+ or negative tumors (P less than 0.05)
  • Survival did not differ significantly between rats with CD146 1+ and CD146-negative tumors (P = 0.44)
  • Rats with IMP3 overexpression (2+ or 3+) had shorter survival than rats with IMP3 0 or 1+ tumors (P less than 0.05)
  • Rats whose tumors were high for both CD146 and IMP3 had shorter survival than rats whose tumors were low for both (P less than 0.01)
  • HIF-1a, cyclin D1 and Ki-67 levels in the rat tumors showed no significant difference in survival
  • In cell lines, CD146 overexpression occurred in only 1 of 6 sarcomatoid lines. IMP3 overexpression was seen in 4 of 4 epithelioid lines and 2 of 6 sarcomatoid lines.
  • Non-tumorous CD146-positive cells with features of myofibroblasts were occasionally seen growing beneath the normal mesothelial layer
• The authors' conclusion: The authors concluded that CD146 and IMP3 are good diagnostic and prognostic markers in mesothelioma, and that this rat model is ideal for studying preventive and therapeutic strategies.
• Limitations the authors state:
  • CD146 also stains blood vessel lining cells and pericytes, so it can be difficult to tell stromal cells from mesothelioma cells
  • Tissue staining did not fully show CD146 and IMP3 in the same locations
  • The authors did not show directly (by co-immunoprecipitation) that IMP3 regulates CD146 in rat mesothelioma

Topics

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

Medical terms in this study, explained in our Lexicon: Prognosis, Mesothelioma, Malignant Mesothelioma, Asbestos Exposure, Chrysotile, Crocidolite, Cell Block, Histological Subtype.

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