Limits...
Collagen VI and hyaluronan: the common role in breast cancer.

Karousou E, D'Angelo ML, Kouvidi K, Vigetti D, Viola M, Nikitovic D, De Luca G, Passi A - Biomed Res Int (2014)

Bottom Line: Collagen VI and hyaluronan are widely distributed extracellular matrix macromolecules that play a crucial role in tissue development and are highly expressed in cancers.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Morphological Sciences, University of Insubria, Via J. H. Dunant 5, 21100 Varese, Italy.

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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4121998&req=5

fig1: 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.

Mentions: As summarized in Figure 1, collagen VI and hyaluronan regulate the breast cancer progression and metastasis and seem to participate in the same biological processes in a synergistic manner. Collagen VI is produced by adipocytes during breast cancer, as well as by macrophages during inflammation. Hyaluronan is mainly produced by stromal cells, even though its increased synthesis by breast cancer cells is correlated to an increased aggressiveness of cancer. Both molecules are responsible for the recruitment of endothelial cells during angiogenesis in the breast cancer microenvironment. Moreover, macrophages produce collagen VI and secrete inflammatory factors that in turn induce hyaluronan synthesis by stromal cells. Both hyaluronan and ETP peptide regulate the trafficking and recruitment of macrophages, demonstrating their synergistic effect in breast cancer progression. Breast cancer is also characterized by EMT process. As discussed above, ETP, hyaluronan, and HAS2 are essential for the induction and maintenance of EMT progression. Thus, simultaneous targeting of these two molecules may be a promising approach for improving pharmaceutical agents and consequently breast cancer treatment.


Collagen VI and hyaluronan: the common role in breast cancer.

Karousou E, D'Angelo ML, Kouvidi K, Vigetti D, Viola M, Nikitovic D, De Luca G, Passi A - Biomed Res Int (2014)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4121998&req=5

fig1: 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.
Mentions: As summarized in Figure 1, collagen VI and hyaluronan regulate the breast cancer progression and metastasis and seem to participate in the same biological processes in a synergistic manner. Collagen VI is produced by adipocytes during breast cancer, as well as by macrophages during inflammation. Hyaluronan is mainly produced by stromal cells, even though its increased synthesis by breast cancer cells is correlated to an increased aggressiveness of cancer. Both molecules are responsible for the recruitment of endothelial cells during angiogenesis in the breast cancer microenvironment. Moreover, macrophages produce collagen VI and secrete inflammatory factors that in turn induce hyaluronan synthesis by stromal cells. Both hyaluronan and ETP peptide regulate the trafficking and recruitment of macrophages, demonstrating their synergistic effect in breast cancer progression. Breast cancer is also characterized by EMT process. As discussed above, ETP, hyaluronan, and HAS2 are essential for the induction and maintenance of EMT progression. Thus, simultaneous targeting of these two molecules may be a promising approach for improving pharmaceutical agents and consequently breast cancer treatment.

Bottom Line: Collagen VI and hyaluronan are widely distributed extracellular matrix macromolecules that play a crucial role in tissue development and are highly expressed in cancers.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Morphological Sciences, University of Insubria, Via J. H. Dunant 5, 21100 Varese, Italy.

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.

Show MeSH
Related in: MedlinePlus