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Title: Secreted phosphoprotein 24 kD (Spp24) inhibits growth of human pancreatic cancer cells caused by BMP-2

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [3];  [4]; ;  [5];  [4];  [6];  [7];  [1];  [4];  [8]
  1. Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing (China)
  2. Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai (China)
  3. Department of Orthodontics, School and Hospital of Stomatology, Xi'an Jiaotong University, Xi'an (China)
  4. Research Service, VA Greater Los Angeles Healthcare System, North Hills, CA (United States)
  5. Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA (United States)
  6. National Institute of Traumatology and Orthopaedics, Rio de Janeiro (Brazil)
  7. Division of Orthopaedic Surgery, Department of Surgery, University of Nevada School of Medicine, Las Vegas, NV (United States)
  8. Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA (United States)

The emerging role of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers has drawn great attention in cancer research. In this study, we report that BMP-2 can promote the proliferation of the pancreatic tumor cell line, PANC-1. Secreted phosphoprotein 24 kD (Spp24), a BMP binding protein, did not affect the proliferation of the cells but promoted the apoptosis of the cells in vitro. In a xeneograft tumor model using PANC-1 cells, BMP-2 dramatically promoted tumor growth, while Spp24 not only abolished the effect of BMP-2, but also dramatically induced tumor shrinking when used alone. Activation of Smad1/5/8 participated in this process as demonstrated by immunohistochemical staining of phosphorylated Smad 1/5/8. We conclude that Spp24 can be developed into a therapeutic agent that could be employed in clinical situations where the inhibition of BMPs and related proteins is advantageous. - Highlights: • Spp24 effectively inhibited the in vivo tumor growth of PANC-1. • BMP-2 dramatically promoted tumor growth by promoting PANC-1 proliferation. • Spp24 abolished the tumor growth effect of BMP-2 by promoting PANC-1 apoptosis. • Spp24 may be a candidate as a therapeutic agent of pancreatic cancer.

OSTI ID:
22592754
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 466, Issue 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English

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