Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers
The deposition of collagen-rich desmoplastic tissue is a well-documented feature of the solid tumor microenvironment (TME). However, efforts to target the desmoplastic extracellular matrix (ECM) en masse, or collagen molecules more specifically, have been met with mixed and sometimes paradoxical res...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/13/3132 |
| _version_ | 1797480715798970368 |
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| author | Ashley M. Fuller Tzipora S. Karin Eisinger-Mathason |
| author_facet | Ashley M. Fuller Tzipora S. Karin Eisinger-Mathason |
| author_sort | Ashley M. Fuller |
| collection | DOAJ |
| description | The deposition of collagen-rich desmoplastic tissue is a well-documented feature of the solid tumor microenvironment (TME). However, efforts to target the desmoplastic extracellular matrix (ECM) en masse, or collagen molecules more specifically, have been met with mixed and sometimes paradoxical results. In this review, we posit that these discrepancies are due—at least in part—to the incredible diversity of the collagen superfamily. Specifically, whereas studies of “collagen-targeting” approaches frequently refer to “collagen” as a single molecule or relatively homogeneous molecular family, 28 individual collagens have been identified in mammalian tissues, each with a unique structure, supramolecular assembly pattern, tissue distribution, and/or function. Moreover, some collagen species have been shown to exert both pro- and anti-neoplastic effects in the desmoplastic TME, even within the same cancer type. Therefore, herein, we describe the diversity of the collagen family in normal tissues and highlight the context-specific roles of individual collagen molecules in desmoplastic tumors. We further discuss how this heterogeneity relates to the variable efficacy of “collagen-targeting” strategies in this setting and provide guidance for future directions in the field. |
| first_indexed | 2024-03-09T22:04:04Z |
| format | Article |
| id | doaj.art-f2481db5b6844cacae3791ff967ddb47 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:04:04Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f2481db5b6844cacae3791ff967ddb472023-11-23T19:44:58ZengMDPI AGCancers2072-66942022-06-011413313210.3390/cancers14133132Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic CancersAshley M. Fuller0Tzipora S. Karin Eisinger-Mathason1Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAAbramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAThe deposition of collagen-rich desmoplastic tissue is a well-documented feature of the solid tumor microenvironment (TME). However, efforts to target the desmoplastic extracellular matrix (ECM) en masse, or collagen molecules more specifically, have been met with mixed and sometimes paradoxical results. In this review, we posit that these discrepancies are due—at least in part—to the incredible diversity of the collagen superfamily. Specifically, whereas studies of “collagen-targeting” approaches frequently refer to “collagen” as a single molecule or relatively homogeneous molecular family, 28 individual collagens have been identified in mammalian tissues, each with a unique structure, supramolecular assembly pattern, tissue distribution, and/or function. Moreover, some collagen species have been shown to exert both pro- and anti-neoplastic effects in the desmoplastic TME, even within the same cancer type. Therefore, herein, we describe the diversity of the collagen family in normal tissues and highlight the context-specific roles of individual collagen molecules in desmoplastic tumors. We further discuss how this heterogeneity relates to the variable efficacy of “collagen-targeting” strategies in this setting and provide guidance for future directions in the field.https://www.mdpi.com/2072-6694/14/13/3132desmoplasiaextracellular matrixtumor microenvironmentstromal depletioncancer-associated fibroblastcollagen biosynthesis |
| spellingShingle | Ashley M. Fuller Tzipora S. Karin Eisinger-Mathason Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers Cancers desmoplasia extracellular matrix tumor microenvironment stromal depletion cancer-associated fibroblast collagen biosynthesis |
| title | Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers |
| title_full | Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers |
| title_fullStr | Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers |
| title_full_unstemmed | Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers |
| title_short | Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers |
| title_sort | context matters response heterogeneity to collagen targeting approaches in desmoplastic cancers |
| topic | desmoplasia extracellular matrix tumor microenvironment stromal depletion cancer-associated fibroblast collagen biosynthesis |
| url | https://www.mdpi.com/2072-6694/14/13/3132 |
| work_keys_str_mv | AT ashleymfuller contextmattersresponseheterogeneitytocollagentargetingapproachesindesmoplasticcancers AT tziporaskarineisingermathason contextmattersresponseheterogeneitytocollagentargetingapproachesindesmoplasticcancers |