Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma

Sandro Jube, Zeyana S. Rivera, Marco E. Bianchi, Amy Powers, Ena Wang, Ian Pagano, Harvey I. Pass, Giovanni Gaudino, Michele Carbone, Haining Yang

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Human malignant mesothelioma is an aggressive and highly lethal cancer that is believed to be caused by chronic exposure to asbestos and erionite. Prognosis for this cancer is generally poor because of late-stage diagnosis and resistance to current conventional therapies. The damage-associated molecular pattern protein HMGB1 has been implicated previously in transformation of mesothelial cells. Here we show that HMGB1 establishes an autocrine circuit in malignant mesothelioma cells that influences their proliferation and survival. Malignant mesothelioma cells strongly expressed HMGB1 and secreted it at high levels in vitro. Accordingly, HMGB1 levels in malignant mesothelioma patient sera were higher than that found in healthy individuals. The motility, survival, and anchorage-independent growth of HMGB1-secreting malignant mesothelioma cells was inhibited in vitro by treatment with monoclonal antibodies directed against HMGB1 or against the receptor for advanced glycation end products, a putative HMGB1 receptor. HMGB1 inhibition in vivo reduced the growth of malignant mesothelioma xenografts in severe-combined immunodeficient mice and extended host survival. Taken together, our findings indicate that malignant mesothelioma cells rely on HMGB1, and they offer a preclinical proof-of-principle that antibody-mediated ablation of HMBG1 is sufficient to elicit therapeutic activity, suggesting a novel therapeutic approach for malignant mesothelioma treatment.

Original languageEnglish
Pages (from-to)3290-3301
Number of pages12
JournalCancer Research
Volume72
Issue number13
DOIs
Publication statusPublished - 1 Jul 2012
Externally publishedYes

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HMGB1 Protein
Neoplasms
Survival
Therapeutics
Malignant Mesothelioma
SCID Mice
Delayed Diagnosis
Asbestos
Growth
Heterografts
Monoclonal Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. / Jube, Sandro; Rivera, Zeyana S.; Bianchi, Marco E.; Powers, Amy; Wang, Ena; Pagano, Ian; Pass, Harvey I.; Gaudino, Giovanni; Carbone, Michele; Yang, Haining.

In: Cancer Research, Vol. 72, No. 13, 01.07.2012, p. 3290-3301.

Research output: Contribution to journalArticle

Jube, S, Rivera, ZS, Bianchi, ME, Powers, A, Wang, E, Pagano, I, Pass, HI, Gaudino, G, Carbone, M & Yang, H 2012, 'Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma', Cancer Research, vol. 72, no. 13, pp. 3290-3301. https://doi.org/10.1158/0008-5472.CAN-11-3481
Jube, Sandro ; Rivera, Zeyana S. ; Bianchi, Marco E. ; Powers, Amy ; Wang, Ena ; Pagano, Ian ; Pass, Harvey I. ; Gaudino, Giovanni ; Carbone, Michele ; Yang, Haining. / Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. In: Cancer Research. 2012 ; Vol. 72, No. 13. pp. 3290-3301.
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