Related Experiment Video
Updated: May 5, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Antisense-mediated reduction in thrombospondin reverses the malignant phenotype of a human squamous carcinoma
Abstract:
Thrombospondin (TSP) is a trimeric glycoprotein which is synthesized and incorporated into the extracellular matrix by a wide variety of cells. TSP is involved in a number of cellular processes which govern tumor cell behavior including mitogenesis, attachment, migration, and differentiation. To directly assess the role of TSP in tumor cell growth and spread, a human squamous carcinoma cell line, with high TSP production and an invasive phenotype, was transfected with a TSP cDNA antisense expression vector. Five unique transfected clones were obtained with reduced TSP production. Expression of the transfected antisense sequence in these clones was verified by a ribonuclease protection assay. These clones demonstrated reduced growth rates in vitro when compared with a vector transfected control. After subcutaneous inoculation into athymic mice, the antisense clones formed either no tumors or tumors that were slow growing and highly differentiated. This contrasted with the vector-transfected clone which produced poorly differentiated, rapidly growing, invasive tumors. Our results argue in favor of a direct role for TSP in determining the malignant phenotype of certain human tumors.
Insights
Thrombospondin (TSP) plays a key role in cancer progression. Reducing TSP levels in squamous carcinoma cells significantly inhibited tumor growth and invasiveness, suggesting TSP drives malignant phenotypes.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Thrombospondin (TSP) is an extracellular matrix glycoprotein involved in cellular processes regulating tumor cell behavior.
- TSP influences mitogenesis, attachment, migration, and differentiation, impacting tumor growth and spread.
Purpose of the Study:
- To investigate the direct role of TSP in the malignant phenotype of human squamous carcinoma.
- To assess how reducing TSP production affects tumor cell growth and invasiveness.
Main Methods:
- A human squamous carcinoma cell line with high TSP production was transfected with a TSP cDNA antisense expression vector.
- Five clones with reduced TSP production were generated and verified using ribonuclease protection assay.
- In vitro growth rates and in vivo tumor formation in athymic mice were analyzed.
Main Results:
- Transfected clones exhibited significantly reduced in vitro growth rates compared to controls.
- Antisense clones formed either no tumors or slow-growing, highly differentiated tumors in vivo.
- Control clones produced rapidly growing, poorly differentiated, and invasive tumors.
Conclusions:
- TSP directly contributes to the malignant phenotype of certain human tumors.
- Reducing TSP expression is a potential therapeutic strategy to inhibit tumor growth and invasiveness.
More Related Videos
07:05TGF-β-mediated Endothelial to Mesenchymal Transition EndMT and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
Published on: February 26, 2021
07:13Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Related Concept Videos
02:15Replicative Cell Senescence
01:12Loss of Tumor Suppressor Gene Functions
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...