Role of extracellular matrix architecture and signaling in melanoma therapeutic resistance

Abstract

The extracellular matrix (ECM) is critical for maintaining tissue homeostasis therefore its production, assembly and mechanical stiffness are highly regulated in normal tissues. However, in solid tumors, increased stiffness resulting from abnormal ECM structural changes is associated with disease progression, an increased risk of metastasis and poor survival. As a dynamic and key component of the tumor microenvironment, the ECM is becoming increasingly recognized as an important feature of tumors, as it has been shown to promote several hallmarks of cancer via biochemical and biomechanical signaling. In this regard, melanoma cells are highly sensitive to ECM composition, stiffness and fiber alignment because they interact directly with the ECM in the tumor microenvironment via cell surface receptors, secreted factors or enzymes. Importantly, seeing as the ECM is predominantly deposited and remodeled by myofibroblastic stromal fibroblasts, it is a key avenue facilitating their paracrine interactions with melanoma cells. This review gives an overview of melanoma and further describes the critical roles that ECM properties such as ECM remodeling, ECM-related proteins and stiffness play in cutaneous melanoma progression, tumor cell plasticity and therapeutic resistance. Finally, given the emerging importance of ECM dynamics in melanoma, future perspectives on therapeutic strategies to normalize the ECM in tumors are discussed.

The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance

“…Over the past decade, the ECM in the tumor microenvironment has been shown to play a key role in the progression and acquisition of therapeutic resistance in melanoma [ 51 , 52 ]. Although TT and ICB have improved overall survival in patients with metastatic cutaneous melanoma [ 27 ], therapeutic resistance, which involves both tumor cell intrinsic mechanisms and extrinsic cues from the tumor microenvironment, constitutes a major hurdle in the successful treatment of melanoma.…”

Engineered live bacteria as disease detection and diagnosis tools

“…Melanoma is the most severe type of skin cancer with a poor prognosis and high mortality rate. Current therapeutic approaches are unable to target tumor cells due to increased stiffness resulting from abnormal extracellular matrix structural changes and a hypoxic tumor environment [ 200 ]. In this regard, the ability of L. lactis to detect melanoma using Multispectral Optoacoustic Tomography (MSOT) was investigated [ 156 ].…”