The good and bad of targeting cancer-associated extracellular matrix

Sabina Sangaletti, Claudia Chiodoni, Claudio Tripodo, Mario P. Colombo

Research output: Contribution to journalReview article

Abstract

The maintenance of tissue homeostasis requires extracellular matrix (ECM) remodeling. Immune cells actively participate in regenerating damaged tissues contributing to ECM deposition and shaping. Dysregulated ECM deposition characterizes fibrotic diseases and cancer stromatogenesis, where a chronic inflammatory state sustains the ECM increase. In cancer, the ECM fosters several steps of tumor progression, providing pro-survival and proliferative signals, promoting tumor cell dissemination via collagen fibers or acting as a barrier to impede drug diffusion. Interfering with processes leading to chronic ECM deposition, as occurring in cancer, might allow the simultaneous targeting of both primary tumors and metastatic lesions. However, a note of caution comes from data showing that defective ECM deposition is associated with an exacerbated inflammatory and autoimmune phenotype and to lymphomagenesis. Immune cells display ITIM-inhibitory receptors recognizing collagens as counter ligands, which negatively regulate the immune response. This is in line with the idea that ECM components can provide homeostatic signals to immune cells to regulate and prevent unwanted activation, a concept particularly relevant in cancer where these mechanisms could be in place to keep infiltrating immune cells in a suppressive pro-tumoral state. In this context, the pharmacological targeting of myeloid cells, for which both direct and indirect roles in ECM deposition have been shown, can be a relevant option to this purpose.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalCurrent Opinion in Pharmacology
Volume35
DOIs
Publication statusPublished - Aug 1 2017

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Extracellular Matrix
Neoplasms
Collagen Receptors
Myeloid Cells
Homeostasis
Collagen
Maintenance
Pharmacology
Ligands
Phenotype
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

The good and bad of targeting cancer-associated extracellular matrix. / Sangaletti, Sabina; Chiodoni, Claudia; Tripodo, Claudio; Colombo, Mario P.

In: Current Opinion in Pharmacology, Vol. 35, 01.08.2017, p. 75-82.

Research output: Contribution to journalReview article

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