Fibrotic tumor stroma plays an important role in facilitating triple-negative breast cancer (TNBC) progression and chemotherapeutic resistance. We previously reported a rationally designed protein (ProAgio) that targets integrin αvβ3 at a novel site. ProAgio induces apoptosis via the integrin. Cancer-associated fibroblasts (CAFs) and angiogenic endothelial cells (aECs) in TNBC tumor express high levels of integrin αvβ3. ProAgio effectively induces apoptosis in CAFs and aECs. The depletion of CAFs by ProAgio reduces intratumoral collagen and decreases growth factors released from CAFs in the tumor, resulting in decreased cancer cell proliferation and apoptotic resistance. ProAgio also eliminates leaky tumor angiogenic vessels, which consequently reduces tumor hypoxia and improves drug delivery. The depletion of CAFs and reduction in hypoxia by ProAgio decreases lysyl oxidase (LOX) secretion, which may play a role in the reduction of metastasis. ProAgio stand-alone or in combination with a chemotherapeutic agent provides survival benefit in TNBC murine models, highlighting the therapeutic potential of ProAgio as a treatment strategy.
Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC
Disclosures: L. Sun reported he owns shares in Amoytop, which exclusively licenses the commercial right of ProAgio in the Chinese market. Z.-R. Liu reported "other" from ProDa BioTech LLC outside the submitted work; in addition, Z.-R. Liu had a patent number 9,175,063 licensed to ProDa BioTech LLC. No other disclosures were reported.
- Views Icon Views
- Share Icon Share
- Search Site
Malvika Sharma, Ravi Chakra Turaga, Yi Yuan, Ganesh Satyanarayana, Falguni Mishra, Zhen Bian, Wei Liu, Li Sun, Jenny Yang, Zhi-Ren Liu; Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC. J Exp Med 5 April 2021; 218 (4): e20200712. doi: https://doi.org/10.1084/jem.20200712
Download citation file: