Related Experiment Video
Updated: Jun 10, 2026
Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
Published on: March 18, 2019
Anti-placental growth factor reduces bone metastasis by blocking tumor cell engraftment and osteoclast
Lieve Coenegrachts1, Christa Maes, Sophie Torrekens
1Laboratory of Experimental Medicine and Endocrinology, Vesalius Research Center, KU Leuven, Belgium.
Abstract:
Treatment of bone metastases is largely symptomatic and is still an unmet medical need. Current therapies mainly target the late phase of tumor-induced osteoclast activation and hereby inhibit further metastatic growth. This treatment method is, however, less effective in preventing initial tumor engraftment, a process that is supposed to depend on the bone microenvironment. We explored whether bone-derived placental growth factor (PlGF), a homologue of vascular endothelial growth factor-A, regulates osteolytic metastasis. Osteogenic cells secrete PlGF, the expression of which is enhanced by bone-metastasizing breast tumor cells. Selective neutralization of host-derived PlGF by anti-mouse PlGF (alphaPlGF) reduced the incidence, number, and size of bone metastases, and preserved bone mass. alphaPlGF did not affect metastatic tumor angiogenesis but inhibited osteoclast formation by preventing the upregulation of the osteoclastogenic cytokine receptor activator of NF-kappaB ligand in osteogenic cells, as well as by blocking the autocrine osteoclastogenic activity of PlGF. alphaPlGF also reduced the engraftment of tumor cells in the bone and inhibited their interaction with matrix components in the metastatic niche. alphaPlGF therefore inhibits not only the progression of metastasis but also the settlement of tumor in the bone. These findings identify novel properties of PlGF and suggest that alphaPlGF might offer opportunities for adjuvant therapy of bone metastasis.
Insights
Researchers found that blocking placental growth factor (PlGF) in mice reduced bone metastasis incidence, size, and number. This novel approach inhibits both metastasis progression and initial tumor cell settlement in bone.
Area of Science:
- Oncology
- Bone Biology
- Metastasis Research
Background:
- Bone metastasis treatment is primarily symptomatic and an unmet medical need.
- Current therapies target late-stage osteoclast activation, with limited efficacy in preventing initial tumor engraftment.
- The bone microenvironment plays a crucial role in tumor metastasis settlement.
Purpose of the Study:
- To investigate the role of bone-derived placental growth factor (PlGF) in regulating osteolytic metastasis.
- To evaluate the therapeutic potential of neutralizing PlGF in a preclinical model.
Main Methods:
- Explored PlGF expression in osteogenic cells and its regulation by breast tumor cells.
- Utilized anti-mouse PlGF (alphaPlGF) antibody to selectively neutralize host-derived PlGF.
- Assessed the impact of alphaPlGF on bone metastasis incidence, size, number, bone mass, tumor angiogenesis, osteoclast formation, and tumor cell engraftment.
Main Results:
- Host-derived PlGF neutralization by alphaPlGF significantly reduced bone metastasis incidence, number, and size.
- alphaPlGF preserved bone mass and did not affect metastatic tumor angiogenesis.
- alphaPlGF inhibited osteoclast formation by downregulating receptor activator of NF-kappaB ligand and blocking PlGF's autocrine activity.
- alphaPlGF reduced tumor cell engraftment and interaction with bone matrix components.
Conclusions:
- PlGF plays a critical role in both the progression and initial settlement of bone metastasis.
- Selective PlGF neutralization represents a promising strategy for adjuvant therapy of bone metastasis.
- alphaPlGF demonstrates potential for preventing and treating bone metastasis by targeting early tumor cell settlement and subsequent progression.
More Related Videos
05:30Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis
Published on: November 8, 2024
06:00Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
Published on: September 13, 2017
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:16TGF - β Signaling Pathway
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...