Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma.

Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Research Abstract Details 

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Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Abstract Text:

Craig D Peacock,Qiuju Wang,Gregory S Gesell,Ian M Corcoran-Schwartz,Evan Jones,Jynho Kim,Wendy L Devereux,Jonathan T Rhodes,Carol A Huff,Philip A Beachy,D Neil Watkins,William Matsui,

The cancer stem cell hypothesis suggests that malignant growth depends on a subset of tumor cells with stem cell-like properties of self-renewal. Because hedgehog (Hh) signaling regulates progenitor cell fate in normal development and homeostasis, aberrant pathway activation might be involved in the maintenance of such a population in cancer. Indeed, mutational activation of the Hh pathway is associated with medulloblastoma and basal cell carcinoma; pathway activity is also critical for growth of other tumors lacking such mutations, although the mechanism of pathway activation is poorly understood. Here we study the role and mechanism of Hh pathway activation in multiple myeloma (MM), a malignancy with a well defined stem cell compartment. In this model, rare malignant progenitors capable of clonal expansion resemble B cells, whereas the much larger tumor cell population manifests a differentiated plasma cell phenotype that pathologically defines the disease. We show that the subset of MM cells that manifests Hh pathway activity is markedly concentrated within the tumor stem cell compartment. The Hh ligand promotes expansion of MM stem cells without differentiation, whereas the Hh pathway blockade, while having little or no effect on malignant plasma cell growth, markedly inhibits clonal expansion accompanied by terminal differentiation of purified MM stem cells. These data reveal that Hh pathway activation is heterogeneous across the spectrum of MM tumor stem cells and their more differentiated progeny. The potential existence of similar relationships in other adult cancers may have important biologic and clinical implications for the study of aberrant Hh signaling.

Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Publishing Authors By Initials

CD Peacock,Q Wang,GS Gesell,IM Corcoran-Schwartz,E Jones,J Kim,WL Devereux,JT Rhodes,CA Huff,PA Beachy,DN Watkins,W Matsui,

For similar heterocyclic compounds: alkaloids: veratrum alkaloids research abstracts see: heterocyclic compounds: alkaloids: veratrum alkaloids research

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Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 4048-53

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 27

MONTH: 02

YEAR: 2007

Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Keywords Mesh Terms:

KEYWORDS: Veratrum Alkaloids

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Information

Substance Name: cyclopamine

Registry Number: 4449-51-8

Grant and Affiliation Information for Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma.

AFFILIATION: Sidney Kimmel Comprehensive Cancer Center and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Country: United States

AGENCY: United States NCI

GRANT: P50 CA 058184

ACRONYM: CA

MEDLINETA: Proc Natl Acad Sci U S A

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