Secreted phosphoprotein 24 kD (Spp24) inhibits the growth of human osteosarcoma through the BMP-2/Smad signaling

Hongfang Chen1, Chenshuang Li2, Tangjun Zhou1

  • 1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Insights

Secreted phosphoprotein 24 kD (Spp24) inhibits osteosarcoma (OS) growth by blocking BMP-2 signaling. This study shows Spp24 has therapeutic potential for skeletal tumors by promoting apoptosis and inhibiting proliferation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Autocrine stimulation drives skeletal tumor growth.
  • Growth factor inhibitors can reduce tumor progression.

Purpose of the Study:

  • Investigate Secreted phosphoprotein 24 kD (Spp24) effects on osteosarcoma (OS) growth.
  • Determine Spp24's role with and without BMP-2 in vitro and in vivo.

Main Methods:

  • Utilized 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay and immunohistochemistry.
  • Employed subcutaneous and intratibial tumor models in nude mice.
  • Analyzed BMP-2/Smad signaling pathway activation.

Main Results:

  • Spp24 inhibited OS cell proliferation and promoted apoptosis.
  • BMP-2 enhanced tumor cell mobility and invasiveness; Spp24 inhibited these effects.
  • Spp24 inhibited BMP-2-induced Smad1/5/8 phosphorylation and Smad8 gene expression.
  • Spp24 significantly inhibited OS tumor growth in vivo.

Conclusions:

  • BMP-2/Smad pathway is crucial in OS pathogenesis.
  • Spp24 inhibits human OS growth induced by BMP-2 via Smad signaling interruption and apoptosis.
  • Spp24 shows potential as a therapeutic agent for OS and skeletal tumors.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.1K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.6K