Digestive Diseases and Sciences

, Volume 55, Issue 6, pp 1516–1524

The Role of Sonic Hedgehog Reemergence During Gastric Cancer

  • Jason Martin
  • Jessica M. Donnelly
  • JeanMarie Houghton
  • Yana Zavros
Review

Abstract

Sonic Hedgehog (Shh) signaling has been extensively studied for its role in developmental biology and cancer biology. The association between Shh and cancer development in general is well established but the functional role of Shh in the development and progression of gastric cancer specifically is largely unknown. Bone marrow-derived stem cells, specifically mesenchymal stem cells (MSCs) infiltrate and engraft into the gastric mucosa in response to the chronic inflammatory environment of Helicobacter infection. In this review, MSC infiltration and changes in the cytokine and cellular profiles of later-stage chronic environments will be tied into their interactions with the Shh pathway. We will discuss how these changes shape tumorigenesis and tumor progression in the gastric mucosa. The current review focuses on the Shh signaling pathway and its role in the development of gastric cancer, specifically in response to Helicobacter pylori infection. We follow with an in-depth discussion of the regulation of the Hedgehog pathway during acute and chronic gastric inflammation with a focus on signaling within the MSC compartment.

Keywords

Gastric cancer Sonic Hedgehog Bone-marrow-derived cells Cancer development 

Abbreviations

Shh

Sonic Hedgehog

Ihh

Indian Hedgehog

Dhh

Desert Hedgehog

Smo

Smoothened

Ptch

Patched

Gli1

Glioma-associated Oncogene homolog 1

Hh

Hedgehog

H. pylori

Helicobacter pylori

Hp

H. pylori

BMDC

Bone-marrow-derived cells

MSCs

Bone-marrow-derived mesenchymal stem cells

CDX2

Caudal-type homeobox transcription factor 2

SDF-1

Stromal-derived factor-1

MDSC

Myeloid-derived suppressor cells

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jason Martin
    • 1
  • Jessica M. Donnelly
    • 1
  • JeanMarie Houghton
    • 2
    • 3
  • Yana Zavros
    • 1
  1. 1.Department of Molecular and Cellular PhysiologyUniversity of Cincinnati College of MedicineCincinnatiUSA
  2. 2.Division of Gastroenterology, Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Department of Cancer BiologyUniversity of Massachusetts Medical SchoolWorcesterUSA

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