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Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers
Ashley M Fuller1, Tzipora S Karin Eisinger-Mathason1
1Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, Penn Sarcoma Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract:
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.
Insights
Tumor microenvironment research reveals collagen diversity. Understanding the 28 distinct collagen types and their varied roles is key to improving cancer therapies targeting the extracellular matrix.
Area of Science:
- Oncology
- Biochemistry
- Extracellular Matrix Biology
Background:
- Desmoplastic tissue deposition is a hallmark of the tumor microenvironment (TME).
- Targeting the extracellular matrix (ECM) or collagen in tumors has yielded inconsistent results.
- The heterogeneity of collagen molecules is a likely reason for these variable outcomes.
Purpose of the Study:
- To review the diversity of the collagen family in normal tissues.
- To highlight the context-specific roles of individual collagen molecules in desmoplastic tumors.
- To explain the variable efficacy of collagen-targeting strategies due to collagen heterogeneity.
Main Methods:
- Literature review of collagen structure, function, and distribution.
- Analysis of individual collagen roles in the desmoplastic TME.
- Synthesis of findings to guide future research in cancer therapy.
Main Results:
- Mammalian tissues contain 28 distinct collagen types with unique structures and functions.
- Individual collagen species can exhibit both pro- and anti-neoplastic effects within the TME.
- Collagen heterogeneity explains the mixed efficacy of current therapeutic strategies.
Conclusions:
- Recognizing the diversity of the collagen superfamily is critical for understanding tumor biology.
- Future therapeutic strategies must account for specific collagen types and their roles in cancer.
- Further research is needed to develop targeted therapies based on collagen heterogeneity.
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