Thrombospondin 1 Triggers Osteosarcoma Cell Metastasis and Tumor Angiogenesis

Yue Kui Jian1, Huan Ye Zhu1, Xing Lin Wu1

  • 1Affiliated People's Hospital of Guizhou Medical University, Guiyang, P.R. China.

Oncology Research
|March 16, 2018
PubMed

Insights

Thrombospondin 1 (TSP-1) effectively inhibits osteosarcoma growth and metastasis by targeting angiogenesis. This discovery offers new therapeutic avenues for patients with limited treatment options.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcomas with metastatic or unresectable disease have limited therapeutic options.
  • Pharmacologic inhibitors of angiogenesis show limited efficacy in osteosarcomas due to rapid tumor resistance, increased invasiveness, and accelerated metastasis.

Purpose of the Study:

  • To investigate the potential of thrombospondin 1 (TSP-1) as an inhibitor of osteosarcoma growth and metastasis.
  • To elucidate the role of the TSP-1/CD36/vasculostatin signaling axis in osteosarcoma angiogenesis.

Main Methods:

  • Overexpression of TSP-1 in the MG-63 osteosarcoma cell line.
  • In vitro angiogenesis assays using MG-63 cells and human umbilical vein endothelial cells (HUVECs).
  • In vivo studies using xenografted osteosarcoma tumor models.

Main Results:

  • TSP-1 overexpression inhibited the growth and metastasis of MG-63 osteosarcoma cells.
  • TSP-1 facilitated the expression of vasculostatin in MG-63 cells.
  • TSP-1 overexpression inhibited angiogenesis and tumor growth in xenograft models in a CD36-dependent manner.

Conclusions:

  • TSP-1 is a potent inhibitor of osteosarcoma growth and metastasis.
  • The TSP-1/CD36/vasculostatin signaling axis plays a critical role in mediating antiangiogenic activity in osteosarcoma.
  • Targeting this axis may offer a novel therapeutic strategy for osteosarcoma treatment.

Related Concept Videos

Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.6K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.9K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.6K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.0K
SN1 Reaction: Stereochemistry02:15

SN1 Reaction: Stereochemistry

This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
10.4K
SN1 Reaction: Kinetics02:05

SN1 Reaction: Kinetics

In an SN2 reaction, the reaction rate depends on both the type of nucleophile and the substrate. A hindered tertiary alkyl halide is practically inert to the SN2 mechanism despite using a strong nucleophile.
However, Sir Christopher Ingold and Edward D. Hughes, who studied the kinetics of various nucleophilic substitution reactions, noticed that a tertiary alkyl halide does undergo a nucleophilic substitution reaction in the presence of a weak nucleophile. While studying the substitution...
9.7K