Progressive growth of a human pleural mesothelioma xenografted to athymic rats and mice

Our plain-English summary of Progressive growth of a human pleural mesothelioma xenografted to athymic rats and mice, by C.J. Lindén, L. Johansson (British Journal of Cancer, 1988).

The study

• Authors: C.J. Lindén, L. Johansson
• Journal: British Journal of Cancer
• Published: 1988;58(5):614-8
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A human malignant pleural mesothelioma was xenografted serially in athymic nude Rowett rats for 27 passages during 33 months. After the two initial passages (P), the take rate during P3-9 was 100% (192/192). The tumour grew progressively during P3-9 in 99% (190/192) and regressed totally in 1% (2/192). The take rate for the tumour xenografted to athymic BALB/c mice was also 100% (17/17) and no regressions were observed. During serial passaging in nude rats, the tumour-volume doubling time (TD) decreased from 6 days in P2 to 3 days in P8-9 (P less than 0.001) and then remained around 3 days during P10-25. A TD of 11 days in P1 (man-mouse) for tumours grown in mice decreased during 10 passages in rats to 4 days (P less than 0.005) when the tumour was transplanted to mice in P11. Light microscopic morphology of the tumour was retained in rats and mice. We believe that our experimental tumour model using the nude rat as a carrier of the xenograft will be useful for studies of human mesothelioma.

In plain English

This was a laboratory animal experiment. The authors took tumour tissue from a 66-year-old man with epithelial-type malignant pleural mesothelioma, whose autopsy showed calcified pleural plaques that the authors said indicated asbestos exposure. They transplanted it under the skin of athymic (immune-deficient) nude rats and mice. The tumour was passed from rat to rat for 27 generations over 33 months. It grew in 13 of 14 rats in the first two passages, 192 of 192 rats in passages 3 to 9, and 17 of 17 mice. Two of 205 tumours in rats regressed completely during passages 1 to 9, and none of 17 did in mice. In rats, the tumour's volume doubling time fell from 6 days in passage 2 to 3 days in passages 8 to 9, then stayed around 3 days through passage 25. Larger tumours doubled faster in rats than in mice (3.6 versus 9.3 days). The tumour kept its microscopic appearance. The authors concluded that the nude rat is a useful and robust carrier for this tumour, including for drug testing.

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: serial transplantation (xenografting) of one human pleural mesothelioma into athymic nude rats and mice
• Who was studied: Tumour from one 66-year-old man with epithelial pleural mesothelioma (tissue taken from an implantation metastasis in needle tracks), grown in congenitally athymic nude Rowett rats and athymic BALB/c mice aged 4-8 weeks, at University Hospital, Lund, Sweden; serially passaged in rats for 27 generations over 33 months
• Exposure: The study did not examine asbestos exposure. The experimental exposure was subcutaneous inoculation of tumour suspension: 1 g in the first passage, 1.6 g in the second rat passage, and 0.5 g from the third passage on. The donor patient's autopsy showed bilateral calcified pleural plaques, which the authors said indicated asbestos exposure.
• Main results:
  • Take rate in rats was 93% (13/14) in the 2 initial passages and 100% (192/192) in passages 3-9. In mice (passages 1 and 11) it was 100% (17/17).
  • 1% (2/205) of tumours growing in rats regressed totally during passages 1-9, and none in mice (0/17). There was no statistically significant difference between rats and mice in take or regression rates.
  • In rats, tumour volume doubling time decreased from 6 days in passage 2 to 3 days in passages 8-9 (P<0.001), then stayed around 3 days in passages 10-25 (P>0.05).
  • In rats, time to reach a tumour volume of 2 cm3 was 36 days in passage 2, 15-16 days in passages 8-9 (P<0.001), and 11-12 days in passages 10-12, with no further decrease through passage 25.
  • At low tumour volume (1-3 cm3), doubling time in mice in passage 11 (4.2 days) was not significantly different from that in rats in passages 10-12 (3.6 days; P=0.03). For tumours larger than 3 cm3, doubling time was shorter in rats (3.6 days) than in mice (9.3 days; P<0.001).
  • In mice, doubling time fell from 11 days in passage 1 to 4 days in passage 11 (after 10 passages in rats; P<0.005). Time to grow to 4 cm3 fell from 79 days to 26 days (P<0.005).
  • The histological pattern was retained in all xenograft generations in rats and mice. Staining was strong or moderate for cytokeratin and EMA and absent for CEA, vimentin and desmin, and this staining pattern was also retained.
• The authors' conclusion: The authors believed the nude rat is a useful and robust carrier of this mesothelioma xenograft, and that the tumour's stable growth in nude rats will make the system useful for experimental studies including drug testing.
• Limitations the authors state:
  • The lowest cell number required for tumour take was not directly assessed. The authors say this would have allowed a more precise evaluation of take rates.
  • Too few mice were inoculated to detect minor differences in regression rates between rats and 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.

Related studies

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• Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice — D.J. Colin, O. Bejuy, et al. (2019)
• Extracellular protease imaging for cell mass tracking of xenografted human malignant pleural mesothelioma — L. Zhou, W. El-Deiry, et al. (2012)
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• Effects of natural interferon alpha, natural tumor necrosis factor alpha and their combination on human mesothelioma xenografts in nude mice — T. Ohnuma, L. Szrajer, et al. (1993)
• Restored expression of the MYO18B gene suppresses orthotopic growth and the production of bloody pleural effusion by human malignant pleural mesothelioma cells in SCID mice — N. Edakuni, K. Ikuta, et al. (2006)

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