Type I collagen turnover is a critical parameter for melanoma progression

Kempen, Léon C van; Rijntjes, Jos; Mamor-Cornelissen, Ine; Vincent‐Naulleau, Silvia; Gerritsen, Marinel; Ruiter, Dirk J.; Dijk, Marcory van; Geffrotin, Claudine; Muijen, Goos van

doi:10.1097/00008390-200609001-00128

Cited by 4 publications

(3 citation statements)

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“…46,47 However, in contrast to carcinomas, melanoma do not induce a strong stromal response with respect to collagen expression and fibroblast activation at the invasive front of deeply invasive melanoma with metastatic capacity. [48][49][50] Collagen expression is mainly confined to the papillary dermis and is reduced upon progression toward deeply invasive tumor growth. Deeply invasive melanomas with metastatic capacity appear thus associated with reduced Col(I) expression in contrast to highly and widespread Col(I) expression in squamous cell carcinoma of the skin.…”

Section: Discussionmentioning

confidence: 99%

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Kempen

Rijntjes

Mamor-Cornelissen

et al. 2007

Intl Journal of Cancer

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Tumors are complex tissues composed of neoplastic cells, soluble and insoluble matrix components and stromal cells. Here we report that in melanoma, turn-over of type I collagen (Col(I)), the predominant matrix protein in dermal stroma affects melanoma progression. Fibroblasts juxtaposed to melanoma cell nests within the papillary dermis display high levels of Col(I) mRNA expression. These nests are enveloped by collagen fibers. In contrast, melanoma-associated fibroblasts within the reticular dermis express Col(I) mRNA at a level that is comparable to its expression in uninvolved dermis and reduced amount of collagen protein can be observed. To determine the significance of Col(I) expression in melanoma, we pharmacologically inhibited its transcription in a porcine cutaneous melanoma model by oral administration of halofuginone. When administered before melanoma development, it reduced melanoma incidence and diminished the transition from microinvasive toward deeply invasive growth by limiting the development of a tumor vasculature. Whereas invasive melanoma growth has been correlated with increased blood vessel density previously, our data for the first time demonstrate that the proangiogenic effect of Col(I) expression by fibroblasts and vascular cells precedes the development of invasive melanomas in a de novo tumor model. ' 2007 Wiley-Liss, Inc.Key words: cutaneous melanoma; type I collagen; angiogenesis; MeLiM porcine melanoma model; halofuginone Tumor development and invasion into adjacent tissue is often accompanied by increased architectural disorder of the extracellular matrix (ECM) and cellular components especially at the invasive front of the neoplastic mass. 1 Along with increased production of extracellular proteolytic enzymes, 2-4 increased synthesis of type I collagen (Col(I)) and other matrix components by stromal cells has been documented in skin, mammary, colon and prostate carcinomas. [5][6][7][8][9] In squamous cell carcinomas of the skin, increased Col(I) synthesis by stromal fibroblasts 9 is also accompanied by enhanced remodeling due to increased activity of matrix proteinases. 10 In contrast, cutaneous melanoma, but with the exception of desmoplastic variants, is not associated with strong ECM remodeling, but is mainly characterized by pericellular proteolysis of Col(I) and elastin at the invasive front. 11 Expression of Col(I) and its contribution to melanoma development and progression have not been studied extensively.In skin, the fibril forming Col(I) is predominantly synthesized by fibroblasts and accounts for 80-90% of the collagenous proteins present in the dermis. 12 Col(I) fibers are composed of righthanded triple helical molecules of 1 Col(I)a2 and 2 Col(I)a1 chains and can be found in all dermal layers. 13 However, the architectural organization of Col(I) fibers is different in the papillary and reticular dermis. Whereas, Col(I) is found as a finely woven meshwork of fibers in the papillary dermis, a distinctive pattern of thick Col(I) bundles is found in reticular dermis.Th...

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Section: Discussionmentioning

confidence: 99%

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Kempen

Rijntjes

Mamor-Cornelissen

et al. 2007

Intl Journal of Cancer

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“…It has also been reported that changes in ECM stiffness is on account of altered collagen I density [18][19][20][21]. In addition, collagen I comprises of 80-90% of the collagenase proteins in the dermis, and studies have showed that altered collagen I density affects melanoma progression in vitro and in vivo [22].…”

Section: Introductionmentioning

confidence: 97%

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments

Higgins

Faatiemah

Peres

et al. 2022

Preprint

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Cell stiffness and TBX3 expression have been identified as biomarkers of melanoma metastasis in 2D environments. This study aimed to determine how mechanical and biochemical properties of melanoma cells change during cluster formation and metastasis in 3D environments mimicking physiological conditions. In isolated cells, mitochondrial fluctuations decreased, and stiffness increased across disease stages and matrix rigidities. TBX3 was overexpressed in soft but diminished in stiff matrices. During cluster formation in soft matrices, the intracellular properties of VGP cells did not change during extensive cluster formation, whereas mitochondrial fluctuations increased and TBX3 expression decreased in MET cells during limited cluster formation. In stiff matrices, cluster formation was restricted, mitochondrial fluctuations and TBX3 expression increased in VGP and MET, and cell stiffness increased in VGP and decreased in MET. Mitochondrial activity, cell stiffness, and TBX3 expression jointly affected cluster formation and metastasis in melanoma, with contributions varying with environmental properties. Hence, biomechanical and biochemical properties of the cells and the environment should be combined to advance targeted cancer therapies.

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“…It has also been reported that ECM stiffness changes are due to altered collagen I density [18][19][20][21]. In addition, collagen I comprises 80-90% of the collagenase proteins in the dermis, and studies have shown that altered collagen I density affects melanoma progression in vitro and in vivo [22].…”

Section: Introductionmentioning

confidence: 98%

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments

Higgins

Faatiemah

Peres

et al. 2023

Experimental Cell Research

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Type I collagen turnover is a critical parameter for melanoma progression

Cited by 4 publications

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Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments

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