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Updated: Jul 6, 2026
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo
B Sharma1, M Handler, I Eichstetter
1Department of Pathology, Anatomy, and Cell Biology, and the Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
Perlecan, a ubiquitous heparan sulfate proteoglycan, possesses angiogenic and growth-promoting attributes primarily by acting as a coreceptor for basic fibroblast growth factor (FGF-2). In this report we blocked perlecan expression by using either constitutive CMV-driven or doxycycline- inducible antisense constructs. Growth of colon carcinoma cells was markedly attenuated upon obliteration of perlecan gene expression and these effects correlated with reduced responsiveness to and affinity for mitogenic keratinocyte growth factor (FGF-7). Exogenous perlecan effectively reconstituted the activity of FGF-7 in the perlecan-deficient cells. Moreover, soluble FGF-7 specifically bound immobilized perlecan in a heparan sulfate-independent manner. In both tumor xenografts induced by human colon carcinoma cells and tumor allografts induced by highly invasive mouse melanoma cells, perlecan suppression caused substantial inhibition of tumor growth and neovascularization. Thus, perlecan is a potent inducer of tumor growth and angiogenesis in vivo and therapeutic interventions targeting this key modulator of tumor progression may improve cancer treatment.
Insights
Perlecan, a proteoglycan, drives tumor growth and blood vessel formation by binding growth factors. Suppressing perlecan significantly inhibits cancer progression and neovascularization in vivo.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Perlecan is a heparan sulfate proteoglycan involved in cell growth and angiogenesis.
- It acts as a coreceptor for fibroblast growth factor 2 (FGF-2).
Purpose of the Study:
- To investigate the role of perlecan in tumor growth and angiogenesis.
- To determine if targeting perlecan can inhibit cancer progression.
Main Methods:
- Perlecan expression was blocked using antisense constructs in colon carcinoma cells.
- Tumor xenografts and allografts were used to assess tumor growth and neovascularization.
- Binding assays were performed to study the interaction between FGF-7 and perlecan.
Main Results:
- Blocking perlecan expression significantly reduced colon carcinoma cell growth.
- Reduced responsiveness and affinity for keratinocyte growth factor (FGF-7) were observed.
- Perlecan suppression inhibited tumor growth and neovascularization in both human colon carcinoma xenografts and mouse melanoma allografts.
- Soluble FGF-7 bound to immobilized perlecan independently of heparan sulfate.
Conclusions:
- Perlecan is a critical inducer of tumor growth and angiogenesis in vivo.
- Targeting perlecan represents a potential therapeutic strategy for cancer treatment.
