Nuclear expression of N-myc downstream regulated gene 1/Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer
Akihiko Kawahara,Jun Akiba,Satoshi Hattori,Tomohiko Yamaguchi,Hideyuki Abe,Tomoki Taira,Hiroki Ureshino,Yuichi Murakami,Kosuke Watari,Kikuo Koufuji,Kazuo Shirouzu,Michihiko Kuwano,Mayumi Ono,Masayoshi Kage +13 more
Reads0
Chats0
TLDR
The expression of NDRG1/Cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of SOTA 1/Ca(2+)-associated protein 43 in the membrane.Abstract:
Expression of N-myc downstream regulated gene 1 (NDRG1)/Ca(2+)-associated protein 43 (Cap43) in cancer cells is a predictive marker of good or poor prognosis depending on tumor type. In this study, we examined whether NDRG1/Cap43 is a marker of good or poor prognosis in gastric cancer patients, and whether it is associated with tumor stromal responses, including angiogenesis and macrophage infiltration. The expression levels of NDRG1/Cap43, the number of CD68-positive macrophages and the CD34-positive microvessel density were analyzed by immunohistochemistry in 129 gastric cancer patients, including 65 with the intestinal type and 64 with the diffuse type. The expression of NDRG1/Cap43 in the nucleus and the membrane was evaluated. Nuclear NDRG1/Cap43 expression was found in 20/65 (30.8%) patients with the intestinal type and in 9/64 (14.1%) patients with the diffuse type of gastric cancer. Nuclear NDRG1/Cap43 expression was significantly associated with pathological stage in the intestinal type (P=0.002), but not in the diffuse type (P=0.039). Nuclear NDRG1/Cap43 expression was also closely associated with infiltrating macrophages (P=0.001) and tumor angiogenesis (P=0.001) in the intestinal type. Furthermore, nuclear NDRG1/Cap43 expression was associated with poor prognosis in both the intestinal (P=0.001) and the diffuse types of gastric cancer (P=0.047). By contrast, membranous NDRG1/Cap43 expression was not associated with the overall survival of gastric cancer patients with either the intestinal or diffuse type of gastric cancer. The expression of NDRG1/Cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of NDRG1/Cap43 in the membrane.read more
Citations
More filters
Journal ArticleDOI
Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy.
Bernard A. M. Fang,Žaklina Kovačević,Kyung Chan Park,Danuta S. Kalinowski,Patric J. Jansson,Darius J.R. Lane,Sumit Sahni,Des R. Richardson +7 more
TL;DR: The role of this important metastasis suppressor is described, the relationship between the molecular structure of this protein and its functions remains unclear and interesting unresolved issues regarding this protein are discussed.
Journal ArticleDOI
Exosomes Derived from Human Primary and Metastatic Colorectal Cancer Cells Contribute to Functional Heterogeneity of Activated Fibroblasts by Reprogramming Their Proteome
TL;DR: This study highlights the role of primary and metastatic CRC tumor‐derived Exos in generating phenotypically and functionally distinct subsets of CAFs that may facilitate tumor progression.
Book
Molecular Functions of the Iron-Regulated Metastasis Suppressor Ndrg1
TL;DR: In this article, the metastasis suppressor, NDRG1, was found to be pleiotropic and largely dependent on the genetic background of the cells examined, and the potential for NDRD1 to be utilized as a molecular target for the treatment of pancreatic cancer using a novel thiosemicarbazone compound.
Journal ArticleDOI
Suppressing N-Myc downstream regulated gene 1 reactivates senescence signaling and inhibits tumor growth in hepatocellular carcinoma
TL;DR: It is demonstrated that NDRG1 is a potential therapeutic target for HCC because its suppression triggers senescence of HCC cells through activating glycogen synthase kinase-3β-p53 pathway, thereby inhibiting tumor progression.
Journal ArticleDOI
Pharmacological targeting and the diverse functions of the metastasis suppressor, NDRG1, in cancer.
TL;DR: The molecular mechanism(s) underlying NDRG1 pleiotropic roles remain elusive, but are linked to differential regulation of WNT signaling and potentially differential interaction with the tumor suppressor, PTEN.
References
More filters
Journal ArticleDOI
The two histological main types of gastric carcinoma; diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification
Journal ArticleDOI
Tumour-educated macrophages promote tumour progression and metastasis
TL;DR: Macrophages are educated by the tumour microenvironment, so that they adopt a trophic role that facilitates angiogenesis, matrix breakdown and tumour-cell motility — all of which are elements of the metastatic process.
Journal ArticleDOI
Distinct Role of Macrophages in Different Tumor Microenvironments
TL;DR: The evidence for differential regulation of TAMs in these microenvironments is discussed and an overview of current attempts to target or use TAMs for therapeutic purposes is provided.
Journal ArticleDOI
Altered macrophage differentiation and immune dysfunction in tumor development
Antonio Sica,Vincenzo Bronte +1 more
TL;DR: A complete understanding of the complex interplay between neoplastic and myelomonocytic cells might offer novel targets for therapeutic intervention aimed at depriving tumor cells of important growth support and enhancing the antitumor immune response.
Journal ArticleDOI
Tumor-associated macrophages press the angiogenic switch in breast cancer
Elaine Y. Lin,Jeffrey W. Pollard +1 more
TL;DR: It is found that tumor-associated macrophages that are recruited to the tumor just before malignant conversion are essential for the angiogenic switch, establishing a causal linkage to explain well-documented clinical correlations between macrophage, microvessel density, and poor prognosis in breast tumors.