Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors
Alteration in glycosylation pattern of MUC1 mucin tandem repeats during carcinomas has been shown to negatively affect adhesive properties of malignant cells and enhance tumor invasiveness and metastasis. In addition, MUC1 overexpression is closely interrelated with angiogenesis, making it a great t...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13123 |
| _version_ | 1819007715308994560 |
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| author | Parnaz Merikhian Behrad Darvishi Neda Jalili Mohammad Reza Esmailinejad Azadeh Sharif Khatibi Shima Moradi Kalbolandi Malihe Salehi Marjan Mosayebzadeh Mahdieh Shokrollahi Barough Keivan Majidzadeh‐A Fatemeh Yadegari Fatemeh Rahbarizadeh Leila Farahmand |
| author_facet | Parnaz Merikhian Behrad Darvishi Neda Jalili Mohammad Reza Esmailinejad Azadeh Sharif Khatibi Shima Moradi Kalbolandi Malihe Salehi Marjan Mosayebzadeh Mahdieh Shokrollahi Barough Keivan Majidzadeh‐A Fatemeh Yadegari Fatemeh Rahbarizadeh Leila Farahmand |
| author_sort | Parnaz Merikhian |
| collection | DOAJ |
| description | Alteration in glycosylation pattern of MUC1 mucin tandem repeats during carcinomas has been shown to negatively affect adhesive properties of malignant cells and enhance tumor invasiveness and metastasis. In addition, MUC1 overexpression is closely interrelated with angiogenesis, making it a great target for immunotherapy. Alongside, easier interaction of nanobodies (single‐domain antibodies) with their antigens, compared to conventional antibodies, is usually associated with superior desirable results. Herein, we evaluated the preclinical efficacy of a recombinant nanobody against MUC1 tandem repeats in suppressing tumor growth, angiogenesis, invasion, and metastasis. Expressed nanobody demonstrated specificity only toward MUC1‐overexpressing cancer cells and could internalize in cancer cell lines. The IC50 values (the concentration at which the nanobody exerted half of its maximal inhibitory effect) of the anti‐MUC1 nanobody against MUC1‐positive human cancer cell lines ranged from 1.2 to 14.3 nm. Similar concentrations could also effectively induce apoptosis in MUC1‐positive cancer cells but not in normal cells or MUC1‐negative human cancer cells. Immunohistochemical staining of spontaneously developed mouse breast tumors prior to in vivo studies confirmed cross‐reactivity of nanobody with mouse MUC1 despite large structural dissimilarities between mouse and human MUC1 tandem repeats. In vivo, a dose of 3 µg nanobody per gram of body weight in tumor‐bearing mice could attenuate tumor progression and suppress excessive circulating levels of IL‐1a, IL‐2, IL‐10, IL‐12, and IL‐17A pro‐inflammatory cytokines. Also, a significant decline in expression of Ki‐67, MMP9, and VEGFR2 biomarkers, as well as vasculogenesis, was evident in immunohistochemically stained tumor sections of anti‐MUC1 nanobody‐treated mice. In conclusion, the anti‐MUC1 tandem repeat nanobody of the present study could effectively overcome tumor growth, invasion, and metastasis. |
| first_indexed | 2024-12-21T00:28:59Z |
| format | Article |
| id | doaj.art-421ed2bec7cd4c90ac362225db1a79b7 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-21T00:28:59Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-421ed2bec7cd4c90ac362225db1a79b72022-12-21T19:21:55ZengWileyMolecular Oncology1574-78911878-02612022-01-0116248550710.1002/1878-0261.13123Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumorsParnaz Merikhian0Behrad Darvishi1Neda Jalili2Mohammad Reza Esmailinejad3Azadeh Sharif Khatibi4Shima Moradi Kalbolandi5Malihe Salehi6Marjan Mosayebzadeh7Mahdieh Shokrollahi Barough8Keivan Majidzadeh‐A9Fatemeh Yadegari10Fatemeh Rahbarizadeh11Leila Farahmand12Recombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranDepartment of Surgery and Radiology Faculty of Veterinary Medicine University of Tehran Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranCancer Immunotherapy and Regenerative Medicine Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranDepartment of Medical Biotechnology Faculty of Medical Sciences Tarbiat Modares University Tehran IranRecombinant Proteins Department Breast Cancer Research Center Motamed Cancer Institute ACECR Tehran IranAlteration in glycosylation pattern of MUC1 mucin tandem repeats during carcinomas has been shown to negatively affect adhesive properties of malignant cells and enhance tumor invasiveness and metastasis. In addition, MUC1 overexpression is closely interrelated with angiogenesis, making it a great target for immunotherapy. Alongside, easier interaction of nanobodies (single‐domain antibodies) with their antigens, compared to conventional antibodies, is usually associated with superior desirable results. Herein, we evaluated the preclinical efficacy of a recombinant nanobody against MUC1 tandem repeats in suppressing tumor growth, angiogenesis, invasion, and metastasis. Expressed nanobody demonstrated specificity only toward MUC1‐overexpressing cancer cells and could internalize in cancer cell lines. The IC50 values (the concentration at which the nanobody exerted half of its maximal inhibitory effect) of the anti‐MUC1 nanobody against MUC1‐positive human cancer cell lines ranged from 1.2 to 14.3 nm. Similar concentrations could also effectively induce apoptosis in MUC1‐positive cancer cells but not in normal cells or MUC1‐negative human cancer cells. Immunohistochemical staining of spontaneously developed mouse breast tumors prior to in vivo studies confirmed cross‐reactivity of nanobody with mouse MUC1 despite large structural dissimilarities between mouse and human MUC1 tandem repeats. In vivo, a dose of 3 µg nanobody per gram of body weight in tumor‐bearing mice could attenuate tumor progression and suppress excessive circulating levels of IL‐1a, IL‐2, IL‐10, IL‐12, and IL‐17A pro‐inflammatory cytokines. Also, a significant decline in expression of Ki‐67, MMP9, and VEGFR2 biomarkers, as well as vasculogenesis, was evident in immunohistochemically stained tumor sections of anti‐MUC1 nanobody‐treated mice. In conclusion, the anti‐MUC1 tandem repeat nanobody of the present study could effectively overcome tumor growth, invasion, and metastasis.https://doi.org/10.1002/1878-0261.13123angiogenesiscancersinvasion and metastasisMUC1nanobodytumor growth |
| spellingShingle | Parnaz Merikhian Behrad Darvishi Neda Jalili Mohammad Reza Esmailinejad Azadeh Sharif Khatibi Shima Moradi Kalbolandi Malihe Salehi Marjan Mosayebzadeh Mahdieh Shokrollahi Barough Keivan Majidzadeh‐A Fatemeh Yadegari Fatemeh Rahbarizadeh Leila Farahmand Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors Molecular Oncology angiogenesis cancers invasion and metastasis MUC1 nanobody tumor growth |
| title | Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors |
| title_full | Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors |
| title_fullStr | Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors |
| title_full_unstemmed | Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors |
| title_short | Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors |
| title_sort | recombinant nanobody against muc1 tandem repeats inhibits growth invasion metastasis and vascularization of spontaneous mouse mammary tumors |
| topic | angiogenesis cancers invasion and metastasis MUC1 nanobody tumor growth |
| url | https://doi.org/10.1002/1878-0261.13123 |
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