Related Experiment Video
Updated: Apr 27, 2026
A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics
Published on: June 16, 2013
TM4SF1: a new vascular therapeutic target in cancer
Chi-Iou Lin1, Anne Merley, Tracey E Sciuto
1The Center for Vascular Biology Research, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RN-280D, Boston, MA, 02215, USA.
Abstract:
Transmembrane-4 L-six family member-1 (TM4SF1) is a small plasma membrane glycoprotein that regulates cell motility and proliferation. TM4SF1 is an attractive cancer target because of its high expression in both tumor cells and on the vascular endothelial cells lining tumor blood vessels. We generated mouse monoclonal antibodies against human TM4SF1 in order to evaluate their therapeutic potential; 13 of the antibodies we generated reacted with extracellular loop-2 (EL2), TM4SF1's larger extracellular, lumen-facing domain. However, none of these antibodies reacted with mouse TM4SF1, likely because the EL2 of mouse TM4SF1 differs significantly from that of its human counterpart. Therefore, to test our antibodies in vivo, we employed an established model of engineered human vessels in which human endothelial colony-forming cells (ECFC) and human mesenchymal stem cells (MSC) are incorporated into Matrigel plugs that are implanted subcutaneously in immunodeficient nude mice. We modified the original protocol by (1) preculturing human ECFC on laminin, fibronectin, and collagen-coated plates, and (2) increasing the ECFC/MSC ratio. These modifications significantly increased the human vascular network in Matrigel implants. Two injections of one of our anti-TM4SF1 EL2 monoclonal antibodies, 8G4, effectively eliminated the human vascular component present in these plugs; they also abrogated human PC3 prostate cancer cells that were incorporated into the ECFC/MSC Matrigel mix. Together, these studies provide a mouse model for assessing tumor xenografts that are supplied by a human vascular network and demonstrate that anti-TM4SF1 antibodies such as 8G4 hold promise for cancer therapy.
Insights
Monoclonal antibodies targeting Transmembrane-4 L-six family member-1 (TM4SF1) effectively eliminated human vascular networks and prostate cancer cells in a novel mouse model, showing promise for cancer therapy.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Transmembrane-4 L-six family member-1 (TM4SF1) is a cell surface glycoprotein implicated in cancer cell motility and proliferation.
- TM4SF1's high expression on tumor cells and tumor vasculature makes it a promising therapeutic target.
- Developing effective antibodies against human TM4SF1 requires appropriate in vivo models.
Purpose of the Study:
- To generate and evaluate the therapeutic potential of mouse monoclonal antibodies targeting human TM4SF1.
- To establish and optimize a mouse model for assessing anti-TM4SF1 antibodies in a human vascularized tumor xenograft.
- To demonstrate the efficacy of anti-TM4SF1 antibodies in eradicating human vasculature and cancer cells in vivo.
Main Methods:
- Generation of mouse monoclonal antibodies against human TM4SF1, focusing on the extracellular loop-2 (EL2) domain.
- Modification of an established engineered human vessel mouse model using specific cell culture techniques and altered cell ratios.
- In vivo testing of anti-TM4SF1 antibody 8G4 in the modified humanized mouse model containing human endothelial colony-forming cells, mesenchymal stem cells, and PC3 prostate cancer cells.
Main Results:
- Thirteen monoclonal antibodies targeting human TM4SF1 EL2 were generated; none reacted with mouse TM4SF1.
- Modified protocols significantly enhanced the formation of human vascular networks within Matrigel implants in mice.
- Two injections of anti-TM4SF1 antibody 8G4 successfully eliminated the human vascular component and abrogated human prostate cancer cells within the model.
Conclusions:
- The study successfully developed a mouse model for evaluating tumor xenografts supported by a human vascular network.
- Anti-TM4SF1 antibodies, exemplified by 8G4, demonstrate significant therapeutic potential for cancer treatment by targeting tumor vasculature.
- Targeting TM4SF1 offers a promising strategy for developing novel cancer therapies.
More Related Videos
08:52Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
Published on: January 19, 2018
09:42Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis
Published on: June 26, 2019
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:57Targeted Cancer Therapies
01:24Regulation of Angiogenesis and Blood Supply
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:56Treatment Resistant Cancers
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...