Title | A potent immunotoxin targeting fibroblast activation protein for treatment of breast cancer in mice. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Fang J, Xiao L, Joo K-I, Liu Y, Zhang C, Liu S, Conti PS, Li Z, Wang P |
Journal | Int J Cancer |
Volume | 138 |
Issue | 4 |
Pagination | 1013-23 |
Date Published | 2016 Feb 15 |
ISSN | 1097-0215 |
Keywords | Animals, Antineoplastic Agents, BALB 3T3 Cells, Breast Neoplasms, Disease Models, Animal, Female, Fibroblasts, Flow Cytometry, Fluorescent Antibody Technique, Gelatinases, Humans, Immunohistochemistry, Immunotoxins, Membrane Proteins, Mice, Real-Time Polymerase Chain Reaction, Serine Endopeptidases |
Abstract | Fibroblast activation protein (FAP) is highly expressed in the tumor-associated fibroblasts (TAFs) of most human epithelial cancers. FAP plays a critical role in tumorigenesis and cancer progression, which makes it a promising target for novel anticancer therapy. However, mere abrogation of FAP enzymatic activity by small molecules is not very effective in inhibiting tumor growth. In this study, we have evaluated a novel immune-based approach to specifically deplete FAP-expressing TAFs in a mouse 4T1 metastatic breast cancer model. Depletion of FAP-positive stromal cells by FAP-targeting immunotoxin αFAP-PE38 altered levels of various growth factors, cytokines, chemokines and matrix metalloproteinases, decreased the recruitment of tumor-infiltrating immune cells in the tumor microenvironment and suppressed tumor growth. In addition, combined treatment with αFAP-PE38 and paclitaxel potently inhibited tumor growth in vivo. Our findings highlight the potential use of immunotoxin αFAP-PE38 to deplete FAP-expressing TAFs and thus provide a rationale for the use of this immunotoxin in cancer therapy. |
DOI | 10.1002/ijc.29831 |
Alternate Journal | Int. J. Cancer |
PubMed ID | 26334777 |
PubMed Central ID | PMC4715643 |
Grant List | P01 CA132681 / CA / NCI NIH HHS / United States P01CA132681 / CA / NCI NIH HHS / United States R01AI068978 / AI / NIAID NIH HHS / United States R01 AI068978 / AI / NIAID NIH HHS / United States P30CA01408 / CA / NCI NIH HHS / United States P30 CA014089 / CA / NCI NIH HHS / United States R01 EB017206 / EB / NIBIB NIH HHS / United States R01 CA170820 / CA / NCI NIH HHS / United States R01CA170820 / CA / NCI NIH HHS / United States R01EB017206 / EB / NIBIB NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm