scholarly journals Osteopontin binds ICOSL promoting tumor metastasis

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Davide Raineri ◽  
Chiara Dianzani ◽  
Giuseppe Cappellano ◽  
Federica Maione ◽  
Gianluca Baldanzi ◽  
...  

Abstract ICOSL/ICOS are costimulatory molecules pertaining to immune checkpoints; their binding transduces signals having anti-tumor activity. Osteopontin (OPN) is here identified as a ligand for ICOSL. OPN binds a different domain from that used by ICOS, and the binding induces a conformational change in OPN, exposing domains that are relevant for its functions. Here we show that in vitro, ICOSL triggering by OPN induces cell migration, while inhibiting anchorage-independent cell growth. The mouse 4T1 breast cancer model confirms these data. In vivo, OPN-triggering of ICOSL increases angiogenesis and tumor metastatization. The findings shed new light on ICOSL function and indicate that another partner beside ICOS may be involved; they also provide a rationale for developing alternative therapeutic approaches targeting this molecular trio.

2014 ◽  
Vol 349 (2) ◽  
pp. 120-127 ◽  
Author(s):  
Lucia Borriello ◽  
Matthieu Montès ◽  
Yves Lepelletier ◽  
Bertrand Leforban ◽  
Wang-Qing Liu ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13510-13510
Author(s):  
S. E. Hahn ◽  
L. A. da Cruz ◽  
D. Sayegh ◽  
A. Ferry ◽  
K. O’Reilly ◽  
...  

13510 Background: CD44 (an adhesion molecule and stem cell antigen), CD59 (a complement-inhibitory molecule), MCSP (an adhesion and cell-cell interactions), and Trop-2 (EpCam a related signaling molecule) represent a group of biologically-significant cancer proteins acting through distinct mechanisms. We have described Abs with in vitro and in vivo cancer suppressive activity to this group of targets. However, their effectiveness depends on the phenotype of malignant cells; cell response should correlate with expression of its Ag, and tumor cells represent a heterogeneous group of non-synchronous cells. The present study describes the efficacy of those antibodies in breast cancer models and the prevalence of their antigen targets in a survey of human breast cancer tissues. Methods: In vivo activity of antibodies ARH460–16–2 (anti-CD44), AR36A36.11.1 (anti-CD59), AR11BD-2E11–2 (anti-MCSP), and AR47A6.4.2 (anti-Trop-2) in estrogen-dependent and hormone sensitive xenograft models of human breast cancer was examined. In addition, distribution of the antigens in breast cancer was determined by immunohistochemistry using tumor tissue arrays of breast cancer sections from distinct patients. Results: Treatment of an established breast cancer model with ARH460–16–2 resulted in 51% median tumor xenograft suppression (p<0.05), as well as increased survival in an MDA-MB-231 (breast cancer) grafted model. 63% of human breast cancer sections expressed the CD44 antigen. Treatment with anti-CD59 antibody AR36A36.11.1 resulted in 68% xenograft tumor suppression (p<0.005). AR47A6.4.2 anti-Trop-2 antibody bound to 100% of human breast cancer sections tested, and showed efficacy in the estrogen- dependent MCF-7 breast cancer model. Anti-MCSP antibody AR11BD-2E11–2 demonstrated 80% tumor growth inhibition (p<0.001), increased survival in an estrogen-dependent model of breast cancer, and was found to stain 62% of breast cancer tissues examined. Conclusions: The heterogeneity of breast cancer cell phenotypes in in vitro and in vivo studies and variable composite cellular antigen targets is the basis for the therapeutic use of multiple antibodies, each with independent mechanisms of action, and offers a rationale for combined antibody therapy in selected patients. [Table: see text]


Nanoscale ◽  
2014 ◽  
Vol 6 (24) ◽  
pp. 15228-15235 ◽  
Author(s):  
Min Zhou ◽  
Geng Ku ◽  
Laura Pageon ◽  
Chun Li

A single-compartment nanoparticle system mediates dual photoacoustic imaging and confined thermolysis for tumor ablation.


2017 ◽  
Vol 36 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Can Huang ◽  
Wenjun Lan ◽  
Feifei Wang ◽  
Chun Zhang ◽  
Xiaomei Liu ◽  
...  

2012 ◽  
Vol 149 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Mohammad Hossein Yazdi ◽  
Mehdi Mahdavi ◽  
Bardia Varastehmoradi ◽  
Mohammad Ali Faramarzi ◽  
Ahmad Reza Shahverdi

2021 ◽  
Author(s):  
Fan Ding ◽  
Chen Huang ◽  
Chenyi Liang ◽  
cheng wang ◽  
Jianjun Liu ◽  
...  

Abstract Purpose: This longitudinal study aims to evaluate the performance of 68 Ga-FAPI-04 and 18 F-FDG and to profile the dynamic process of tumor metastasis in a preclinical 4T1 breast cancer model. Although both of these two radioligands are wildly used in clinic, no study was reported on their performance in the longitudinal monitoring of tumor metastasis. Also, no correlation between the expression level of fibroblast activation protein (FAP) and the development of tumor metastasis has been elucidated previously. In this study, we evaluated the performance of 68 Ga-FAPI-04 and 18 F-FDG PET during the entire process of tumor metastasis, and their potential for the early diagnosis of tumor metastasis. We also clarified the correlation of uptakes as well as the signal-to-background (S/B) ratios between these two probes at different stages of tumor metastasis. Methods: Forty 4T1 metastatic breast cancer murine model were established using female BALB/c mice, followed by the longitudinal imaging with 68 Ga-FAPI-04 and 18 F-FDG once a week for up to six weeks. In vitro Hematoxylin & Eosin (H&E) and immunochemistry (IHE) staining were performed to evaluate FAP expression on the metastatic lesions. Further statistical analysis was performed to evaluate the correlation of 68 Ga-FAPI-04 and 18 F-FDG uptake (%ID/cc) at different stages of the metastasis. Results: 68 Ga-FPAI-04 holds an advantage over 18 F-FDG with higher sensitivity at the early stage of tumor metastasis. However, with the progress of tumor metastasis, uptake of 68 Ga-FAPI-04 decreases and becomes less sensitive than 18 F-FDG. There is also no direct correlation between uptake or S/B ratios of 68 Ga-FAPI-04 and 18 F-FDG during this dynamic process. Conclusion: 68 Ga-FAPI-04 is more sensitive than 18 F-FDG in detecting the early stage of tumor metastasis, but becomes less sensitive than 18 F-FDG at the late stage of tumor metastasis. We envision this result would be meaningful for the explanation of the 18 Ga-FAPI-04 and 18 F-FDG imaging both in the future clinic and preclinic studies.


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