Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer

Mimeault Murielle, Surinder Kumar Batra

Research output: Contribution to journalReview article

120 Citations (Scopus)

Abstract

Multifunctional macrophage inhibitory cytokine-1, MIC-1, is a member of the transforming growth factor-β (TGF-β) superfamily that plays key roles in the prenatal development and regulation of the cellular responses to stress signals and inflammation and tissue repair after acute injuries in adult life. The stringent control of the MIC-1 expression, secretion, and functions involves complex regulatory mechanisms and the interplay of other growth factor signaling networks that control the cell behavior. The deregulation of MIC-1 expression and signaling pathways has been associated with diverse human diseases and cancer progression. The MIC-1 expression levels substantially increase in cancer cells, serum, and/or cerebrospinal fluid during the progression of diverse human aggressive cancers, such as intracranial brain tumors, melanoma, and lung, gastrointestinal, pancreatic, colorectal, prostate, and breast epithelial cancers. Of clinical interest, an enhanced MIC-1 expression has been positively correlated with poor prognosis and patient survival. Secreted MIC-1 cytokine, like the TGF-β prototypic member of the superfamily, may provide pleiotropic roles in the early and late stages of carcinogenesis. In particular, MIC-1 may contribute to the proliferation, migration, invasion, metastases, and treatment resistance of cancer cells as well as tumor-induced anorexia and weight loss in the late stages of cancer. Thus, secreted MIC-1 cytokine constitutes a new potential biomarker and therapeutic target of great clinical interest for the development of novel diagnostic and prognostic methods and/or cancer treatment against numerous metastatic, recurrent, and lethal cancers.

Original languageEnglish (US)
Pages (from-to)626-635
Number of pages10
JournalJournal of Cellular Physiology
Volume224
Issue number3
DOIs
StatePublished - Sep 1 2010

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Growth Differentiation Factor 15
Transforming Growth Factors
Tumors
Cells
Cytokines
Cerebrospinal fluid
Oncology
Deregulation
Biomarkers
Brain
Neoplasms
Intercellular Signaling Peptides and Proteins
Repair
Tissue
Behavior Control
Anorexia
Brain Neoplasms
Cerebrospinal Fluid
Disease Progression
Weight Loss

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer. / Murielle, Mimeault; Batra, Surinder Kumar.

In: Journal of Cellular Physiology, Vol. 224, No. 3, 01.09.2010, p. 626-635.

Research output: Contribution to journalReview article

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