Secreted phosphoprotein 24 kD (Spp24) inhibits growth of human pancreatic cancer cells caused by BMP-2.
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.
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, PR China.
Chen-Shuang
CS
Li
Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, PR China; Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA; Department of Surgery, Bethune School of Medics, Shijiazhuang, PR China. Electronic address: haijuntianmd@gmail.com.
Haijun
H
Tian
Department of Orthodontics, School and Hospital of Stomatology, Xi'an Jiaotong University, Xi'an, PR China.
Min
M
Zou
Research Service, VA Greater Los Angeles Healthcare System, North Hills, CA, USA.
Ke-Wei
KW
Zhao
Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
Yawei
Y
Li
Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
Lifeng
L
Lao
Research Service, VA Greater Los Angeles Healthcare System, North Hills, CA, USA; Geriatric Research, Education and Clinical Center, VA Greater Los Angeles Healthcare System, North Hills, CA, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Elsa J
EJ
Brochmann
National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
M Eugenia L
ME
Duarte
Division of Orthopaedic Surgery, Department of Surgery, University of Nevada School of Medicine, Las Vegas, NV, USA.
Michael D
MD
Daubs
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, PR China. Electronic address: yanhengzhou@vip.163.com.
Yan-Heng
YH
Zhou
Research Service, VA Greater Los Angeles Healthcare System, North Hills, CA, USA; Geriatric Research, Education and Clinical Center, VA Greater Los Angeles Healthcare System, North Hills, CA, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Samuel S
SS
Murray
Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA, USA.
Jeffrey C
JC
Wang
D017209:Apoptosis; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010750:Phosphoproteins / Q000502:physiology*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D010750:Phosphoproteins; C091340:secreted phosphoprotein 24
Bone morphogenetic proteins-2; Pancreatic cancer; Secreted phosphoprotein 24 kD