HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Role of chitinase 3-like-1 and semaphorin 7a in pulmonary melanoma metastasis.

Abstract
The prototypic chitinase-like protein Chi3l1 is induced in cancers and portends a poor prognosis, but whether it contributes to cancer progression is unknown. To address this gap in knowledge, we investigated the production of Chi3l1 in melanoma lung metastases. We found that Chi3l1 was induced during pulmonary melanoma metastasis and that this induction was regulated by the semaphorin Sema7a, interacting in stimulatory or inhibitory ways with its β1 integrin or Plexin C1 receptors, respectively. In mouse strains with genetic deletions of Chi3l1 or Sema7a, there was a significant reduction in pulmonary metastasis. Notably, antiserum raised against Chi3l1 or Sema7a phenocopied the reduction produced by genetic deletions. Melanoma lung metastasis was also decreased in the absence of IL13Rα2, a recently identified receptor for Chi3l1, consistent with a key role for Chi3l1 in melanoma spread. We confirmed roles for Sema7a and Chi3l1 in pulmonary metastasis of EMT6 breast cancer cells. Taken together, our studies establish a novel pathway through which Sem7a and its receptors regulate Chi3l1, revealing a host axis involving IL13Rα2 that plays a critical role in generating a pulmonary microenvironment that is critical to license metastasis.
AuthorsBing Ma, Erica L Herzog, Chun Geun Lee, Xueyan Peng, Chang-Min Lee, Xiaosong Chen, Sara Rockwell, Ja Seok Koo, Harriet Kluger, Roy S Herbst, Mario Sznol, Jack A Elias
JournalCancer research (Cancer Res) Vol. 75 Issue 3 Pg. 487-96 (Feb 1 2015) ISSN: 1538-7445 [Electronic] United States
PMID25511377 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright©2014 American Association for Cancer Research.
Chemical References
  • Antigens, CD
  • Glycoproteins
  • Sema7a protein, mouse
  • Semaphorins
  • chitinase 3-like 1, mouse
Topics
  • Animals
  • Antigens, CD (metabolism)
  • Cell Line, Tumor
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Glycoproteins (metabolism)
  • Immunohistochemistry
  • Lung Neoplasms (metabolism, secondary)
  • Melanoma (metabolism, pathology)
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Semaphorins (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: