Collagen VI and hyaluronan: the common role in breast cancer

Abstract

Collagen VI and hyaluronan are widely distributed extracellular matrix macromolecules that play a crucial role in tissue development and are highly expressed in cancers. Both hyaluronan and collagen VI are upregulated in breast cancer, generating a microenvironment that promotes tumour progression and metastasis. A growing number of studies show that these two molecules are involved in inflammation and angiogenesis by recruiting macrophages and endothelial cells, respectively. Additionally, collagen VI induces epithelial-mesenchymal transition that is correlated to increased synthesis of hyaluronan in mammary cells. Hyaluronan has also a specific role in cellular functions that depends mainly on the size of the polymer, whereas the effect of collagen VI in tumour progression may be the result of the intact molecule or the C5 peptide of α3(VI) chain, known as endotrophin. Collectively, these findings strongly support the parallel role of these molecules in tumour progression and suggest that they may be used as prognostic factors for the breast cancer treatment.

Figure 1

Schematic representation of collagen VI/ETP and hyaluronan contribution in breast cancer progression. Synthesis of collagen VI by adipocytes as well as synthesis of hyaluronan by stromal cells is increased in breast tumour. Macrophages release TGFβ and collagen VI than in turn increase HAS2 and hyaluronan in mammal cells and induce epithelial-mesenchymal transition (EMT). Increased hyaluronan and cleaved ETP induce recruitment of both macrophages and endothelial cells, resulting in neovascularisation that in turn promotes metastasis. This latter phenomenon is also induced by low molecular weight hyaluronan that is the result of HYAL activity on the HMW molecule. Both collagen VI and HMW-hyaluronan induce growth tumour. Abbreviations: ETP, endotrophin; TGFβ, transforming growth factor-beta; HMW-HA and LMW-HA: high and low molecular weight hyaluronan, respectively; HYAL: hyaluronidase; HAS: hyaluronan synthase; TAM: tumour-associated macrophages.