Related Experiment Video

Updated: Nov 10, 2025

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.9K

The tumor suppressive role of TIMP3 in the human osteosarcoma cells

Bingyi Tan1, Xiqiang Xu1, Qingyu Zhang1

  • 1Department of Orthopaedics, Shangdong Provincial Hospital Affiliated to Shandong First Medical University, PR China.

Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association
|April 5, 2021
PubMed
Abstract

Insights

Tissue inhibitor of metalloproteinase 3 (TIMP3) acts as a tumor suppressor in osteosarcoma. Restoring TIMP3 function may offer a new therapeutic strategy for this bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tissue inhibitor of metalloproteinase 3 (TIMP3) regulates cell proliferation, viability, apoptosis, and motility.
  • Loss of TIMP3 function is observed in various human cancers, but its role in osteosarcoma (OS) is not well understood.

Purpose of the Study:

  • To investigate the mechanism by which TIMP3 influences the growth and aggressiveness of human osteosarcoma cells.
  • To explore the cellular and molecular pathways modulated by TIMP3 in osteosarcoma.

Main Methods:

  • Overexpression of TIMP3 in U2OS and 143B human OS cell lines.
  • Assessment of matrix metalloproteinase (MMP) activity.
  • Evaluation of cell proliferation, survival, apoptosis, and chemo-sensitivity.
  • Analysis of tumor cell invasion and the PI3K/AKT signaling pathway.

Main Results:

  • TIMP3 overexpression inhibited endogenous MMP activity and repressed oncogenic phenotypes, including proliferation and survival.
  • TIMP3 induced apoptosis and enhanced sensitivity to cisplatin chemotherapy, independent of MMP inhibition.
  • TIMP3 suppressed tumor cell invasion and modulated oncogenesis by inducing PTEN, leading to PI3K/AKT pathway inactivation.

Conclusions:

  • TIMP3 functions as an oncosuppressor in human osteosarcoma.
  • Reactivating TIMP3 may represent a potential therapeutic approach for osteosarcoma treatment.

More Related Videos

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma08:07

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma

Published on: April 12, 2019

7.4K
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro08:04

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro

Published on: March 18, 2014

13.0K

Related Concept Videos

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...
4.8K
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...
4.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.4K
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...
4.5K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.5K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.4K