scholarly journals A Combination of Cabozantinib and Radiation Does Not Lead to an Improved Growth Control of Tumors in a Preclinical 4T1 Breast Cancer Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Norman Reppingen ◽  
Alexander Helm ◽  
Laura Doleschal ◽  
Marco Durante ◽  
Claudia Fournier
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Lung Metastases ◽  
Growth Control ◽  
Clonogenic Survival ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
4T1 Cells

The tyrosine kinase inhibitor Cabozantinib has been applied in clinical studies in combination with radiotherapy. We investigated the effect of such combination on triple-negative 4T1 cells as a metastatic breast cancer model in vitro and in vivo upon inoculation in BALB/c mice. In vitro assays indicated a potential for improved effects using the combination. Both Cabozantinib (2.5 µM) and 10 Gy of 250 kV x-rays were able to cease the growth of 4T1 cells as revealed by growth curves. In a clonogenic survival assay, the effect of Cabozantinib added on the effects of irradiation and the effectiveness of inhibiting the clonogenic survival was found to be 2 (RBE10). Additionally, cell death measurements of apoptosis plus necrosis revealed a synergistic effect when combining irradiation with Cabozantinib. Surprisingly, however, in vivo tumor growth kinetics showed no additional effect in growth control when irradiation was used together with Cabozantinib. Since both ionizing radiation and Cabozantinib are acknowledged to feature immunogenic effects, we additionally investigated the effect of the treatments on lung metastases. No difference to the control groups was found here, neither for irradiation nor Cabozantinib alone nor in combination. Yet, upon analysis of the mice’ livers, CD11b-positive cells, indicating immune suppressive myeloid derived suppressor cells were found diminished following treatment with Cabozantinib. In conclusion, despite promising in vitro controls of the combination of Cabozantinib and irradiation, tumor growth control was not increased by the combination, which was true also for the occurrence of lung metastases.

scholarly journals Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model

2012 ◽  
Vol 33 (4) ◽  
pp. 523-530 ◽  
Author(s):  
Li-hua Lai ◽  
Qi-hong Fu ◽  
Yang Liu ◽  
Kai Jiang ◽  
Qing-ming Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Tumor Growth And Metastasis

Therapeutic monoclonal antibodies target phenotypically-differing human breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13510-13510
Author(s):  
S. E. Hahn ◽  
L. A. da Cruz ◽  
D. Sayegh ◽  
A. Ferry ◽  
K. O’Reilly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
In Vivo Studies ◽  
Tumor Growth Inhibition ◽  
Cancer Model ◽  
Human Breast ◽  
Breast Cancer Model ◽  
Cancer Tissues

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]

Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model

2014 ◽  
Vol 349 (2) ◽  
pp. 120-127 ◽  
Author(s):  
Lucia Borriello ◽  
Matthieu Montès ◽  
Yves Lepelletier ◽  
Bertrand Leforban ◽  
Wang-Qing Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Anti Tumor Activity

Establishment of a Human Breast Cancer Model by Fusion PCR for In Vivo and In Vitro Fluorescence Imaging of Human Breast Cancer

2017 ◽  
Vol 36 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Can Huang ◽  
Wenjun Lan ◽  
Feifei Wang ◽  
Chun Zhang ◽  
Xiaomei Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fluorescence Imaging ◽  
Human Breast Cancer ◽  
Cancer Model ◽  
Human Breast ◽  
Fusion Pcr ◽  
Breast Cancer Model

scholarly journals Osteopontin binds ICOSL promoting tumor metastasis

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Davide Raineri ◽  
Chiara Dianzani ◽  
Giuseppe Cappellano ◽  
Federica Maione ◽  
Gianluca Baldanzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Metastasis ◽  
Immune Checkpoints ◽  
Cancer Model ◽  
Therapeutic Approaches ◽  
Breast Cancer Model ◽  
4T1 Breast Cancer ◽  
Anti Tumor Activity

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.

Sign in / Sign up

Export Citation Format

Share Document