Stromal reaction in cutaneous melanoma

Labrousse, A.; Ntayi, Carole; Hornebeck, William; Bernard, Philippe

doi:10.1016/j.critrevonc.2003.10.007

Critical Reviews in Oncology/Hematology

2004

DOI: 10.1016/j.critrevonc.2003.10.007

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Stromal reaction in cutaneous melanoma

A. Labrousse

Carole Ntayi

William Hornebeck

et al.

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Cited by 49 publications

(35 citation statements)

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“…This is an important finding, given that the inhibition of type I collagen synthesis in melanoma advanced stages can contribute to further progression of the tumor and its degradation by metalloproteinases is associated with tumor invasiveness. 52,53 These assumptions may support a link between the results of the histological analysis and our findings regarding the metastasis evaluation in which the LDE-PTX and Simva treatment resulted in marked reduction of animals with metastasis, while PTX and Simva was ineffective. In fact, monotherapy with LDE-PTX also showed the ability to reduce metastasis development, although to a lower degree than the combined therapy with LDE-PTX and Simva.…”

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confidence: 64%

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Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Kretzer¹,

Maria²,

Guido³

et al. 2016

IJN

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Purpose Lipid nanoemulsions (LDEs) that bind to low-density lipoprotein (LDL) receptors used as carriers of paclitaxel (PTX) can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva), which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX). Materials and methods B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls), Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 μmol/kg (three intraperitoneal injections, 3 alternate days): Simva 50 mg/kg/day by gavage, 9 consecutive days. Results Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and myelosuppression. Conclusion Simva increased the antitumor activity of PTX carried in LDE but not of PTX commercial presentation, possibly because statins increase the expression of LDL receptors that internalize LDE-PTX.

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supporting

confidence: 64%

“…51,52 In tumors excised from the LDE-PTX and Simva group, the effect of the treatment in reducing the number of neoplastic cells was markedly greater than in those excised from the commercial PTX and Simva group. Furthermore, LDE-PTX and Simva was the only treatment that increased the presence of collagen fibers in the tumor stroma.…”

mentioning

confidence: 99%

Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Kretzer¹,

Maria²,

Guido³

et al. 2016

IJN

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“…11 Melanoma cells interact with their environment not only by direct cell-cell contact, but also through the release of cytokines and growth factors. These by autocrine and paracrine effects enable them to grow autonomously and confer competence to metastasis.…”

mentioning

confidence: 99%

Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma

Dua

Ingle

Gude

2007

Intl Journal of Cancer

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Rapid tumor growth and metastasis are 2 major problems associated with treatment of malignant melanoma. Therefore, drugs that can intervene these processes are of clinical importance. Pentoxifylline (PTX), a methyl xanthine derivative, has been shown to inhibit B16F10 melanoma tumor growth and metastasis. We hypothesized that suramin when combined with PTX enhances its antineoplastic effects, which we have examined using the B16F10 mouse melanoma model. Suramin in simultaneous or sequential combination potentiated the cytotoxic effects of PTX on B16F10 cells. PTX arrested cells in the G0-G1 phase and suramin augmented the effects. Both the drugs inhibited F10 adhesion to laminin, matrigel and collagen type IV and showed enhanced inhibition in combination The combination also demonstrated significantly higher inhibition in cell motility (p 5 0.002) and invasion through matrigel (p 5 0.005) as compared to the single agents. Suramin synergized with PTX in its effects on secretion of MMP-9 gelatinase. DBA2/J mice implanted with intradermal B16F10 tumor were used as a model to study tumor growth. Animals were intratumorally treated with 50 mg/kg of PTX, 10 mg/kg of suramin and their combinations. Simultaneous administration of the drugs inhibited tumor growth by 5-to 6-folds. Tumor growth was completely blocked in sequential regimen with regression in some cases. The number and size of metastatic nodules on lung was also reduced significantly by the combination treatment. In conclusion, the novel combination of PTX and suramin has synergistic antitumor and antimetastatic activity in B16F10 melanoma and may be a promising approach in treatment of patients suffering from malignant melanoma. ' 2007 Wiley-Liss, Inc.Key words: pentoxifylline; suramin; B16F10 melanoma; metastasis; combination therapy Malignant melanoma is the deadliest form of skin cancer, and its incidence has shown a 6-fold increase since the past 2 to 3 decades.1 There is no standard treatment for patients with metastatic melanoma. Treatment options include the surgical resection of isolated metastases, therapy with dacarbazine, and immunotherapy. However, response rates associated with these measures range between 15 and 20%, and hence there is an urgent need for the development of new therapies. The success of antimetastatic therapy depends on inhibition of diverse stimuli produced by the tumor and its microenvironment while limiting overall toxicity. Thus it has been suggested that a combination of antimetastatic compounds may be more effective than monotherapies.In our earlier reports we have demonstrated that pentoxifylline (PTX), a methyl xanthine derivative inhibits B16F10 melanoma solid tumor growth and metastasis to lung, 3 which is mediated via its inhibitory action on cell adhesion, MMP-9 and -2 secretion, 4 and tumor angiogenesis.5 PTX has been used to enhance tumor sensitivity to both radiation 6 and alkylating agents 7 because of its antioxidant nature and its property to abrogate the G2-M checkpoint, respectively. It has also been reporte...

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“…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.…”

mentioning

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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Stromal reaction in cutaneous melanoma

Cited by 49 publications

References 56 publications

Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma

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

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