Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells-Potential Links with Sarcomas

Our plain-English summary of Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells-Potential Links with Sarcomas, by D.L. Pouliquen, A. Boissard, C. Henry, et al (Cancers, 2020).

The study

• Authors: D.L. Pouliquen, A. Boissard, C. Henry, S. Blandin, P. Richomme, O. Coqueret, C. Guette
• Journal: Cancers
• Published: 2020;12(11)
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Investigations of liver metastatic colonization suggest that the microenvironment is preordained to be intrinsically hospitable to the invasive cancer cells. To identify molecular determinants of that organotropism and potential therapeutic targets, we conducted proteomic analyses of the liver in an aggressive model of sarcomatoid peritoneal mesothelioma (M5-T1). The quantitative changes between SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra) proteotype patterns of the liver from normal rats (G1), adjacent non-tumorous liver from untreated tumor-bearing rats (G2), and liver from curcumin-treated rats without hepatic metastases (G3) were compared. The results identified 12 biomarkers of raised immune response against M5-T1 cells in G3 and 179 liver biomarker changes in (G2 vs. G1) and (G3 vs. G2) but not in (G3 vs. G1). Cross-comparing these 179 candidates with proteins showing abundance changes related to increasing invasiveness in four different rat mesothelioma tumor models identified seven biomarkers specific to the M5-T1 tumor. Finally, analysis of correlations between these seven biomarkers, purine nucleoside phosphorylase being the main biomarker of immune response, and the 179 previously identified proteins revealed a network orchestrating liver colonization and treatment efficacy. These results highlight the links between potential targets, raising interesting prospects for optimizing therapies against highly invasive cancer cells exhibiting a sarcomatoid phenotype and sarcoma cells.

In plain English

This was an animal experiment in Fischer F344 rats using a laboratory model of sarcomatoid peritoneal mesothelioma. The tumor cells, called M5-T1, came from a cell line the authors describe as established from a male rat after 378 days of induction with crocidolite fibers injected into the peritoneal (abdominal) cavity. The tumor-bearing rats in this study were injected with these cells, not with fibers. Using stored liver tissue, the authors compared liver proteins in three groups: two normal rats, eight untreated tumor-bearing rats, and four tumor-bearing rats that had responded to repeated intraperitoneal injections of curcumin. They detected 1411 proteins. Of these, 179 changed in untreated rats compared with both other groups but showed no statistically significant difference between treated and normal rats. Seven proteins were linked specifically to the M5-T1 tumor. Treated rats had more lymphocytes in the liver. One immune-related enzyme, purine nucleoside phosphorylase, changed in opposite directions in treated and untreated rats compared with normal rats. The authors concluded that their data suggest curcumin produces protein changes accounting for its antitumor effects.

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: proteomic (SWATH-MS) comparison of stored, paraffin-embedded liver tissue from rats with an experimental sarcomatoid peritoneal mesothelioma, with and without curcumin treatment, plus histology of liver lymphocytes
• Who was studied: Fischer F344 rats: two normal rats (Control, G1), eight untreated rats bearing the M5-T1 tumor (Tumor, G2), and four curcumin-treated rats bearing the M5-T1 tumor without liver metastases (Tumor + Curcumin, G3), selected from four of six treated rats that responded to treatment
• Exposure: The tumor-bearing groups (Tumor and Tumor + Curcumin) received an intraperitoneal injection of the M5-T1 sarcomatoid mesothelioma cell line. The normal control rats did not. The authors describe this cell line as originating from a male F344 rat after 378 days of induction with crocidolite fibers injected intraperitoneally. The treated group also received repeated intraperitoneal injections of curcumin.
• Main results:
  • 1411 proteins were detected in each liver sample.
  • The number of proteins with statistically significant differences was 439 for untreated tumor-bearing rats vs normal rats, 549 for untreated vs curcumin-treated rats, and 355 for curcumin-treated vs normal rats.
  • 179 proteins changed significantly in untreated rats compared with both normal and treated rats, but showed no statistically significant difference between treated and normal rats: 61 decreased and 118 increased.
  • Among 12 immune-response biomarkers, purine nucleoside phosphorylase (PNPH) was the only one changing differently in curcumin-treated and untreated rats relative to normal rats.
  • Lymphocyte counts were increased in the livers of curcumin-treated rats.
  • Seven proteins were found to be common to liver colonization and specifically to the M5-T1 tumor (listed later as COR1A, CNN3, HS71B, RPN1, SMAD3, TRY1 and TRY3).
  • Within the untreated group, only TRY1 and TRY3 of these seven proteins differed significantly between initial and advanced tumor stages (four rats each).
• The authors' conclusion: The authors concluded that their data suggest curcumin produces changes in liver proteins that account for its antitumor effects in this rat model, including changes favoring an immune response.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Sarcoma, Sarcomatoid, Peritoneal Mesothelioma.

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