Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis

Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
The American Association for Cancer Research (AACR)
Published 2018
Publication Date:
2018-01-17
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
_version_ 1836398751790399488
autor Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
beschreibung Purpose: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAb). Experimental Design: Cadherin 17 (CDH17) fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation, and invasion assays using cell lines from different cancer types (colorectal, pancreatic, melanoma, and breast cancer). Effects of the mAbs on cell signaling were determined by Western blot analysis. Nude mice were used for survival analysis after treatment with RGD-specific mAbs and metastasis development. Results: Antibodies against full-length CDH17 failed to block the binding to α2β1 integrin. However, CDH17 RGD peptides generated highly selective RGD mAbs that blocked CDH17 and vascular-endothelial (VE)-cadherin–mediated β1 integrin activation in melanoma and breast, pancreatic, and colorectal cancer cells. Antibodies provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the integrin signaling pathway activation of FAK in colorectal cancer, of JNK and ERK kinases in colorectal and pancreatic cancers, and of JNK, ERK, Src, and AKT in melanoma and breast cancer. In vivo , RGD-specific mAbs increased mouse survival after inoculation of melanoma and colorectal cancer cell lines to cause lung and liver metastasis, respectively. Conclusions: Blocking the interaction between RGD cadherins and α2β1 integrin with highly selective mAbs constitutes a promising therapy against advanced metastatic disease in colon cancer, melanoma, and, potentially, other cancers. Clin Cancer Res; 24(2); 433–44. ©2017 AACR . See related commentary by Marshall, p. 253
citation_standardnr 6139907
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feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-01-17
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/2/433?rss=1
search_space articles
shingle_author_1 Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
shingle_author_2 Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
shingle_author_3 Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
shingle_author_4 Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
shingle_catch_all_1 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
Purpose: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAb). Experimental Design: Cadherin 17 (CDH17) fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation, and invasion assays using cell lines from different cancer types (colorectal, pancreatic, melanoma, and breast cancer). Effects of the mAbs on cell signaling were determined by Western blot analysis. Nude mice were used for survival analysis after treatment with RGD-specific mAbs and metastasis development. Results: Antibodies against full-length CDH17 failed to block the binding to α2β1 integrin. However, CDH17 RGD peptides generated highly selective RGD mAbs that blocked CDH17 and vascular-endothelial (VE)-cadherin–mediated β1 integrin activation in melanoma and breast, pancreatic, and colorectal cancer cells. Antibodies provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the integrin signaling pathway activation of FAK in colorectal cancer, of JNK and ERK kinases in colorectal and pancreatic cancers, and of JNK, ERK, Src, and AKT in melanoma and breast cancer. In vivo , RGD-specific mAbs increased mouse survival after inoculation of melanoma and colorectal cancer cell lines to cause lung and liver metastasis, respectively. Conclusions: Blocking the interaction between RGD cadherins and α2β1 integrin with highly selective mAbs constitutes a promising therapy against advanced metastatic disease in colon cancer, melanoma, and, potentially, other cancers. Clin Cancer Res; 24(2); 433–44. ©2017 AACR . See related commentary by Marshall, p. 253
Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
Purpose: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAb). Experimental Design: Cadherin 17 (CDH17) fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation, and invasion assays using cell lines from different cancer types (colorectal, pancreatic, melanoma, and breast cancer). Effects of the mAbs on cell signaling were determined by Western blot analysis. Nude mice were used for survival analysis after treatment with RGD-specific mAbs and metastasis development. Results: Antibodies against full-length CDH17 failed to block the binding to α2β1 integrin. However, CDH17 RGD peptides generated highly selective RGD mAbs that blocked CDH17 and vascular-endothelial (VE)-cadherin–mediated β1 integrin activation in melanoma and breast, pancreatic, and colorectal cancer cells. Antibodies provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the integrin signaling pathway activation of FAK in colorectal cancer, of JNK and ERK kinases in colorectal and pancreatic cancers, and of JNK, ERK, Src, and AKT in melanoma and breast cancer. In vivo , RGD-specific mAbs increased mouse survival after inoculation of melanoma and colorectal cancer cell lines to cause lung and liver metastasis, respectively. Conclusions: Blocking the interaction between RGD cadherins and α2β1 integrin with highly selective mAbs constitutes a promising therapy against advanced metastatic disease in colon cancer, melanoma, and, potentially, other cancers. Clin Cancer Res; 24(2); 433–44. ©2017 AACR . See related commentary by Marshall, p. 253
Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
Purpose: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAb). Experimental Design: Cadherin 17 (CDH17) fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation, and invasion assays using cell lines from different cancer types (colorectal, pancreatic, melanoma, and breast cancer). Effects of the mAbs on cell signaling were determined by Western blot analysis. Nude mice were used for survival analysis after treatment with RGD-specific mAbs and metastasis development. Results: Antibodies against full-length CDH17 failed to block the binding to α2β1 integrin. However, CDH17 RGD peptides generated highly selective RGD mAbs that blocked CDH17 and vascular-endothelial (VE)-cadherin–mediated β1 integrin activation in melanoma and breast, pancreatic, and colorectal cancer cells. Antibodies provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the integrin signaling pathway activation of FAK in colorectal cancer, of JNK and ERK kinases in colorectal and pancreatic cancers, and of JNK, ERK, Src, and AKT in melanoma and breast cancer. In vivo , RGD-specific mAbs increased mouse survival after inoculation of melanoma and colorectal cancer cell lines to cause lung and liver metastasis, respectively. Conclusions: Blocking the interaction between RGD cadherins and α2β1 integrin with highly selective mAbs constitutes a promising therapy against advanced metastatic disease in colon cancer, melanoma, and, potentially, other cancers. Clin Cancer Res; 24(2); 433–44. ©2017 AACR . See related commentary by Marshall, p. 253
Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
Purpose: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAb). Experimental Design: Cadherin 17 (CDH17) fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation, and invasion assays using cell lines from different cancer types (colorectal, pancreatic, melanoma, and breast cancer). Effects of the mAbs on cell signaling were determined by Western blot analysis. Nude mice were used for survival analysis after treatment with RGD-specific mAbs and metastasis development. Results: Antibodies against full-length CDH17 failed to block the binding to α2β1 integrin. However, CDH17 RGD peptides generated highly selective RGD mAbs that blocked CDH17 and vascular-endothelial (VE)-cadherin–mediated β1 integrin activation in melanoma and breast, pancreatic, and colorectal cancer cells. Antibodies provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the integrin signaling pathway activation of FAK in colorectal cancer, of JNK and ERK kinases in colorectal and pancreatic cancers, and of JNK, ERK, Src, and AKT in melanoma and breast cancer. In vivo , RGD-specific mAbs increased mouse survival after inoculation of melanoma and colorectal cancer cell lines to cause lung and liver metastasis, respectively. Conclusions: Blocking the interaction between RGD cadherins and α2β1 integrin with highly selective mAbs constitutes a promising therapy against advanced metastatic disease in colon cancer, melanoma, and, potentially, other cancers. Clin Cancer Res; 24(2); 433–44. ©2017 AACR . See related commentary by Marshall, p. 253
Bartolome, R. A., Aizpurua, C., Jaen, M., Torres, S., Calvino, E., Imbaud, J. I., Casal, J. I.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
shingle_title_2 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
shingle_title_3 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
shingle_title_4 Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
timestamp 2025-06-30T23:32:04.178Z
titel Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
titel_suche Monoclonal Antibodies Directed against Cadherin RGD Exhibit Therapeutic Activity against Melanoma and Colorectal Cancer Metastasis
topic WW-YZ
uid ipn_articles_6139907