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Malu · 2025-04-21T05:56:45.740Z

Cancer-associated fibroblasts • Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma. CAFs are composed of multiple functionally distinct subtypes that display an enormous plasticity. CAFs exert pleiotropic and opposing functions within the TME. • CAFs synthesize and remodel the ECM, which changes the mechanical properties of the ECM and alters the behavior of cancer cells and immune cells. CAFs impact angiogenesis, and they have a strong immunomodulatory capacity and contribute to immune evasion of cancer. ECM • The ECM is a non-cellular structural component of the TME and comprises a network of fibrous proteins, such as collagens, glycoproteins, and proteoglycans. The ECM is a dynamic structure that is continuously remodeled by proteases produced by a variety of cells in the TME. The composition of matrisomal proteins in the ECM varies between tumor types and stages. • The ECM facilitates intercellular communication in the TME by acting as a reservoir for the sequestration of secreted molecules and as a substrate for cell adhesion and migration. • ECM remodeling by proteases liberates tethered molecules, thus generating localized high concentrations of released mediators. Cancer and TME cells directly contact the surrounding ECM via receptors including integrins and CD44, which form part of the diverse signaling networks that are activated in cancer. Adipocytes • Adipocytes are present in numerous tissues, and they are specialized in storing energy as fat. Obesity is a key risk factor for multiple cancer types. Cancer-associated adipocytes are emerging key contributors to cancer types. • They release free fatty acids, hormones, cytokines, adipokines, and growth factors that impact cancer cells as well as host cells in the TME. There is active interchange of metabolites and amino acids between adipocytes and cancer cells. • Cancer-associated adipocytes have strong immunoregulatory capacity. They contribute to pro-tumorigenic low-grade chronic inflammation by producing chemoattractants for myeloid cells. Neurons and nerves • Neurons and nerve fibers are present in the TME. Accumulating evidence demonstrates that neurons contribute to tumorigenesis. Perineural invasion (PNI) is a process by which cancer cells locally extend along nerves, which is observed in several solid cancer types and is associated with poor outcomes. • Moreover, there is active crosstalk between neurons and cancer cells in the TME via reciprocal paracrine signaling. • Neurons release neurotransmitters, neurotrophins, and chemokines, which stimulate cancer stemness, resistance to apoptosis, and enhanced proliferation. Moreover, nerves regulate inflammation and immune response in the TME, in the central nervous system, and in extracranial organs and is an active field of cancer research.

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Malu

2d

Edited: 1d

Stromal cells and matrix : TME

in Niveditha

Cancer-associated fibroblasts

Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma. CAFs are composed of multiple functionally distinct subtypes that display an enormous plasticity. CAFs exert pleiotropic and opposing functions within the TME.

CAFs synthesize and remodel the ECM, which changes the mechanical properties of the ECM and alters the behavior of cancer cells and immune cells. CAFs impact angiogenesis, and they have a strong immunomodulatory capacity and contribute to immune evasion of cancer.

ECM

The ECM is a non-cellular structural component of the TME and comprises a network of fibrous proteins, such as collagens, glycoproteins, and proteoglycans. The ECM is a dynamic structure that is continuously remodeled by proteases produced by a variety of cells in the TME. The composition of matrisomal proteins in the ECM varies between tumor types and stages.

The ECM facilitates intercellular communication in the TME by acting as a reservoir for the sequestration of secreted molecules and as a substrate for cell adhesion and migration.

ECM remodeling by proteases liberates tethered molecules, thus generating localized high concentrations of released mediators. Cancer and TME cells directly contact the surrounding ECM via receptors including integrins and CD44, which form part of the diverse signaling networks that are activated in cancer.

Adipocytes

Adipocytes are present in numerous tissues, and they are specialized in storing energy as fat. Obesity is a key risk factor for multiple cancer types. Cancer-associated adipocytes are emerging key contributors to cancer types.

They release free fatty acids, hormones, cytokines, adipokines, and growth factors that impact cancer cells as well as host cells in the TME. There is active interchange of metabolites and amino acids between adipocytes and cancer cells.

Cancer-associated adipocytes have strong immunoregulatory capacity. They contribute to pro-tumorigenic low-grade chronic inflammation by producing chemoattractants for myeloid cells.

Neurons and nerves

Neurons and nerve fibers are present in the TME. Accumulating evidence demonstrates that neurons contribute to tumorigenesis. Perineural invasion (PNI) is a process by which cancer cells locally extend along nerves, which is observed in several solid cancer types and is associated with poor outcomes.

Moreover, there is active crosstalk between neurons and cancer cells in the TME via reciprocal paracrine signaling.

Neurons release neurotransmitters, neurotrophins, and chemokines, which stimulate cancer stemness, resistance to apoptosis, and enhanced proliferation. Moreover, nerves regulate inflammation and immune response in the TME, in the central nervous system, and in extracranial organs and is an active field of cancer research.