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Int J Clin Exp Pathol 2013;6(7):1400-1408

Original Article
The expression patterns of gremlin 1 and noggin in normal adult and tumor tissues

Riikka Laurila, Seppo Parkkila, Jorma Isola, Anne Kallioniemi, Emma-Leena Alarmo

Institute of Biomedical Technology, University of Tampere and BioMediTech, Tampere, Finland; Fimlab Laboratories, Tampere, Finland
Received May 15, 2013; Accepted May 30, 2013; Epub June 15, 2013; Published July 1, 2013

Abstract: Gremlin 1 and noggin are inhibitors of bone morphogenetic protein (BMP) signaling. They are vital during early development but their
role in adult tissues has remained largely unresolved. The BMP signaling pathway has also been implicated in tumorigenesis, however with
emphasis on the role of the ligands and receptors. We performed a concurrent survey of gremlin 1 and noggin protein expression in multiple
normal and cancer samples, using immunohistochemistry on tissue microarrays containing 96 samples from 34 different normal
organs/tissue sites and 208 samples of 34 different tumor types. In majority of both normal and tumor samples, gremlin 1 and noggin
expression was negative or weak. However, normal stomach and skin demonstrated distinct gremlin 1 and noggin expression indicating a role
in adult tissues. Likewise, strong expression of both antagonists was detected in Leydig cells of testis. In the tumor panel, the expression
patterns were more variable but elevated BMP antagonist expression was detected for the first time in few cases, such as glioblastoma,
hepatocellular carcinoma and diffuse B-cell lymphoma for gremlin 1 and renal granular cell tumor and thyroid papillary carcinoma for noggin.
Even though gremlin 1 and noggin were not widely expressed in adult tissues, in a subset of organs their expression pattern indicated a
potential role in normal tissue homeostasis as well as in malignancies. (IJCEP1305022).

Keywords: Gremlin 1, noggin, cancer, normal tissue, immunohistochemistry

Address correspondence to: Dr. Emma-Leena Alarmo, Institute of Biomedical Technology, FIN-33014 University of Tampere, Finland. Tel:
+358 3 31174058; Fax: +358 3 31174168; E-mail: emma-leena.alarmo@uta.fi