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Breast Cancer Cells in Three-dimensional Culture Display an Enhanced Radioresponse after Coordinate Targeting of Integrin α5β1 and Fibronectin
Open accessPublished version of a preprint
Abstract
Tactics to selectively enhance cancer radioresponse are of great interest. Cancer cells actively elaborate and remodel their extracellular matrix (ECM) to aid in survival and progression. Previous work has shown that β1-integrin inhibitory antibodies can enhance the growth-inhibitory and apoptotic responses of human breast cancer cell lines to ionizing radiation, either when cells are cultured in three-dimensional laminin-rich ECM (3D lrECM) or grown as xenografts in mice. Here, we show that a specific α heterodimer of β1-integrin preferentially mediates a prosurvival signal in human breast cancer cells that can be specifically targeted for therapy. 3D lrECM culture conditions were used to compare α-integrin heterodimer expression in malignant and nonmalignant cell lines. Under these conditions, we found that expression of α5β1-integrin was upregulated in malignant cells compared with nonmalignant breast cells. Similarly, we found that normal and oncofetal splice variants of fibronectin, the primary ECM ligand of α5β1-integrin, were also strikingly upregulated in malignant cell lines compared with nonmalignant acini. Cell treatment with a peptide that disrupts the interactions of α5β1-integrin with fibronectin promoted apoptosis in malignant cells and further heightened the apoptotic effects of radiation. In support of these results, an analysis of gene expression array data from breast cancer patients revealed an association of high levels of α5-integrin expression with decreased survival. Our findings offer preclinical validation of fibronectin and α5β1-integrin as targets for breast cancer therapy. Cancer Res; 70(13); 5238–48. ©2010 AACR.
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“Nam et al. demonstrated that human breast cancer cells in 3D culture overexpressed a cell adhesion molecule a 5 b 1-integrin compared to nonmalignant cells, which can be specifically targeted for therapy. 66”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [66]
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“They then found a small peptide inhibitor that can prevent a 5 b 1integrin from binding to fibronectin, thus increases the cell killing effect of radiation.”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [66]
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Cites
Molecular portraits of human breast tumours
Perou, C. M., Sørlie, T., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., Rees, C. A., Pollack, J. R., Ross, D. T., Johnsen, H., Akslen, L. A., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,697
Sørlie, T., Perou, C. M., Tibshirani, R. J., Aas, T., Geisler, S. B., Johnsen, H., Hastie, T. J., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191367098 · Cited by 11,534
Hynes (2002) · doi:10.1016/s0092-8674(02)00971-6 · Cited by 8,606
A Gene-Expression Signature as a Predictor of Survival in Breast Cancer
van de Vijver, M. J., He, Y. D., Veer, L. V. ‘., Dai, H. A., Hart, A. A. M., Voskuil, D. W., Schreiber, G. J., Peterse, J. L., Roberts, C., Marton, M. J., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021967 · Cited by 6,474
AKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115
New Perspectives in Cell Adhesion: RGD and Integrins
Ruoslahti, E. I., & Pierschbacher, M. D. (1987) · Science · doi:10.1126/science.2821619 · Cited by 4,875
A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes
Neve, R. M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F. L., Fevr, T., Clark, L., Bayani, N., Coppé, J., Tong, F. K., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.008 · Cited by 3,224
Taking Cell-Matrix Adhesions to the Third Dimension
Cukierman, E., Pankov, R., Stevens, D. R., & Yamada, K. M. (2001) · Science · doi:10.1126/science.1064829 · Cited by 3,027
The urokinase-type plasminogen activator system in cancer metastasis: A review
Andreasen, P. A., Kjøller, L., Christensen, L., & Duffy, M. J. (1997) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19970703)72:1 · Cited by 1,546
Three-dimensional culture models of normal and malignant breast epithelial cells
Lee, G. Y., Kenny, P. A., Lee, E. H., & Bissell, M. J. (2007) · Nature Methods · doi:10.1038/nmeth1015 · Cited by 1,336
Self-citationPETERSEN, O. W., Rønnov‐Jessen, L., Howlett, A. R., & Bissell, M. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9064 · Cited by 1,096
Self-citationDamiano, J. S., Cress, A. E., Hazlehurst, L., Shtil, A. A., & Dalton, W. S. (1999) · Blood · doi:10.1182/blood.v93.5.1658 · Cited by 899
Aota, S., Nomizu, M., & Yamada, K. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31456-4 · Cited by 637
Zhang, Z., Vuori, K., Reed, J. C., & Ruoslahti, E. I. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.13.6161 · Cited by 626
Tissue Geometry Determines Sites of Mammary Branching Morphogenesis in Organotypic Cultures
Nelson, C. M., VanDuijn, M. M., Inman, J. L., Fletcher, D. A., & Bissell, M. J. (2006) · Science · doi:10.1126/science.1131000 · Cited by 616
Self-citationJarnagin, W. R., Rockey, D. C., Koteliansky, V., Wang, S. S., & Bissell, D. M. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.127.6.2037 · Cited by 452
Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments
Caswell, P. T., Spence, H. J., Parsons, M., White, D. P., Clark, K., Cheng, K. W., Mills, G. B., Humphries, M. J., Messent, A., Anderson, K. I., et al. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.08.012 · Cited by 387
Loss of E-Cadherin Promotes Ovarian Cancer Metastasis via α5-Integrin, which Is a Therapeutic Target
Sawada, K., Mitra, A. K., Radjabi, A. R., Bhaskar, V., Kistner, E. O., Tretiakova, M., Jagadeeswaran, S., MONTAG, A. G., Becker, A. R., Kenny, H. A., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5167 · Cited by 368
Brown, L. F., Guidi, A. J., Schnitt, S. J., Water, L. V. D., Iruela‐Arispe, M. L., Yeo, T. K., Tognazzi, K., & Dvorak, H. F. (1999) · PubMed · Cited by 365
Park, C. C., Zhang, H., Pallavicini, M., Gray, J. W., Baehner, F., Park, C. J., & Bissell, M. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3071 · Cited by 326
Self-citationVARTIO, T., Laitinen, L., Närvänen, O., Cutolo, M., Thornell, L.-E., Zardi, L., & Virtanen, I. (1987) · Journal of Cell Science · doi:10.1242/jcs.88.4.419 · Cited by 247
Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer
Yao, E. S., Zhang, H., Chen, Y., Lee, B., Chew, K., Moore, D. A., & Park, C. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2768 · Cited by 227
Self-citationStoeltzing, O., Liu, W., Reinmuth, N., Fan, F., Parry, G. C., Parikh, A. A., McCarty, M. F., Bucana, C. D., Mazar, A. P., & Ellis, L. M. (2003) · International Journal of Cancer · doi:10.1002/ijc.10958 · Cited by 224
β1 Integrin Inhibition Dramatically Enhances Radiotherapy Efficacy in Human Breast Cancer Xenografts
Park, C. C., Zhang, H. J., Yao, E. S., Park, C. J., & Bissell, M. J. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6390 · Cited by 220
Self-citationKhalili, P., Arakelian, A., Chen, G., Plunkett, M. L., Beck, I., Parry, G. C., Doñate, F., Shaw, D. E., Mazar, A. P., & Rabbani, S. A. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0100 · Cited by 210
Abdollahi, A., Griggs, D. W., Zieher, H., Roth, A. K., Lipson, K. E., Saffrich, R., Gröne, H., Hallahan, D. E., Reisfeld, R. A., Debus, J., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1223 · Cited by 205
The fibronectin gene as a model for splicing and transcription studies
Kornblihtt, A. R., Pesce, C. G., Alonso, C. R., Cramer, P., Srebrow, A., Werbajh, S., & Muro, A. F. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.2.8641558 · Cited by 203
Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2
Liu, H., Radisky, D. C., Nelson, C. M., Zhang, H., Fata, J. E., Roth, R. A., & Bissell, M. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511342103 · Cited by 203
Self-citationTumor cell invasiveness correlates with changes in integrin expression and localization
Macho‐Maschler, S., Wirl, G., Spring, H., Bredow, D. V., Sordat, I., Beug, H., & Ernst Reichmann, A. (2005) · Oncogene · doi:10.1038/sj.onc.1208423 · Cited by 190
Cordes, N., Seidler, J. F., Durzok, R., Geinitz, H., & Brakebusch, C. (2005) · Oncogene · doi:10.1038/sj.onc.1209164 · Cited by 155
Hodkinson, P. S., Elliott, T., Wong, W. S., Rintoul, R. C., MacKinnon, A. C., Haslett, C., & Sethi, T. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401849 · Cited by 144
Mao, Y., & Schwarzbauer, J. E. (2005) · Journal of Cell Science · doi:10.1242/jcs.02566 · Cited by 136
Integrin α5β1 Promotes Survival of Growth-Arrested Breast Cancer Cells
Korah, R. M., Boots, M., & Wieder, R. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3853 · Cited by 131
Cordes, N., & Meineke, V. (2003) · Strahlentherapie und Onkologie · doi:10.1007/s00066-003-1074-4 · Cited by 130
Angiogenesis blockade as a new therapeutic approach to experimental colitis
Danese, S., Sans, M., Spencer, D. M., Beck, I., Doñate, F., Plunkett, M. L., de la Motte, C., Redline, R. W., Shaw, D. E., Levine, A. D., et al. (2006) · Gut · doi:10.1136/gut.2006.114314 · Cited by 130
Manabe, R., Oh-e, N., & Sekiguchi, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.9.5919 · Cited by 117
Livant, D. L., Brabec, R. K., Pienta, K. J., Allen, D. L., Kurachi, K., Markwart, S. M., & Upadhyaya, A. (2000) · PubMed · Cited by 116
Epithelial-derived Fibronectin Expression, Signaling, and Function in Intestinal Inflammation
Kolachala, V. L., Bajaj, R., Wang, L., Yan, Y., Ritzenthaler, J. D., Gewirtz, A. T., Roman, J., Merlin, D., & Sitaraman, S. V. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704388200 · Cited by 91
Deregulation of Alternative Splicing of Fibronectin Pre-mRNA in Malignant Human Liver Tumors
Oyama, F., Hirohashi, S., Shimosato, Y., Titani, K., & Sekiguchi, K. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81621-0 · Cited by 88
Cordes, N., Bläse, M., Meineke, V., & Beuningen, D. V. (2002) · International Journal of Radiation Biology · doi:10.1080/09553000110117340 · Cited by 87
A Cytological Study of the Alimentary Tract of the Domestic Fowl (Gallus domesticus)
Chodnik, K. S. (1947) · Journal of Cell Science · doi:10.1242/jcs.s3-88.4.419 · Cited by 78
Role of alpha 5 beta 1 integrin in determining malignant properties of colon carcinoma cells.
Gong, J., Wang, D., Sun, L., Zborowska, E., Willson, J. K. V., & Brattain, M. G. (1997) · PubMed · Cited by 73
Johnson, G. E., Ivanov, V. N., & Hei, T. K. (2008) · APOPTOSIS · doi:10.1007/s10495-008-0212-y · Cited by 72
Maglott, A., Bartík, P., Coşgun, S., Klotz, P., Rondé, P., Fuhrmann, G., Takeda, K., Martin, S., & Dontenwill, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4105 · Cited by 71
Ionizing radiation induces heritable disruption of epithelial cell interactions
Park, C. C., Henshall-Powell, R. L., Erickson, A., Talhouk, R., Parvin, B., Bissell, M. J., & Barcellos‐Hoff, M. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1832185100 · Cited by 71
Self-citationOnoda, J. M., Piechocki, M. P., & Honn, K. V. (1992) · Radiation Research · doi:10.2307/3578372 · Cited by 59
Saito, T., Kimura, M., Kawasaki, T., Sato, S., & Tomita, Y. (1996) · British Journal of Cancer · doi:10.1038/bjc.1996.57 · Cited by 45
Combination of integrin siRNA and irradiation for breast cancer therapy
Cao, Q., Cai, W., Li, T., Yang, Y., Chen, K., Xing, L., & Chen, X. S. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.100 · Cited by 37
Sandal, T., Valyi‐Nagy, K., Spencer, V. A., Folberg, R., Bissell, M. J., & Maniotis, A. J. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060922 · Cited by 31
Self-citationNing, S., Chen, Z., Dirks, A. J., Husbeck, B., Hsu, M., Bedogni, B., O’Neill, M. S., Powell, M. B., & Knox, S. J. (2007) · Radiation Research · doi:10.1667/rr0829.1 · Cited by 21
Integrin α5 is involved in fibronectin-induced human extravillous trophoblast invasion
Zeng, B.-X., Fujiwara, H., Sato, Y., Nishioka, Y., Yamada, S., Yoshioka, S., Ueda, M., Higuchi, T., & Fujii, S. (2006) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2006.05.007 · Cited by 19
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Henke, E., Nandigama, R., & Ergün, S. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00160 · Cited by 1,142
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Metadata
- Authors
- Nam, J.-M., Onodera, Y., Bissell, M. J., & Park, C. C.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Park, Catherine C.
- Venue
- Cancer Research
- Published
- 2010-06-30
- Volume
- 70
- Issue
- 13
- Pages
- 5238-5248
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2933183
- OpenAlex
- W2146322233
- Cited by
- 196
- References
- 51
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 11 · 2021: 9 · 2020: 15 · 2019: 11 · 2018: 21 · 2017: 18 · 2016: 11 · 2015: 15 · 2014: 14 · 2013: 20 · 2012: 14
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- University of North Texas Digital Library (University of North Texas) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (22700868)
- National Cancer Institute (R01CA124891, U54CA126552, U54CA143836, R37CA064786, U01CA143233, R01CA057621, U54CA112970)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- breast cancer, alpha5beta1 integrin, fibronectin, radiation response, 3D cell culture, integrin heterodimers, apoptosis, integrin-targeted therapy, patient survival
- MeSH terms
- Breast Neoplasms, Female, Fibronectins, Humans, Infrared Rays, Middle Aged, Peptides, Tumor Cells, Cultured, Up-Regulation, Gene Expression, Apoptosis, Cell Culture Techniques, Protein Isoforms, Integrin alpha5beta1, Integrin alpha5, Cell Line, Tumor, Oncogene Protein v-akt
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