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High doses of laser phototherapy can increase proliferation in melanoma stromal connective tissue

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Abstract

It is well established that laser phototherapy (LP) is contraindicated directly over cancer cells, due to its bio modulatory effects in cell and blood vessel proliferation. The aim of the present study was to analyze the influence of typical low-level laser therapy (LLLT) and high intensity laser therapy (HILT) and an in-between dose of 9 J on collagen fibers and blood vessels content in melanoma tumors (B16F10) implanted in mice. Melanoma tumor cells were injected in male Balb C mice which were distributed in four groups: control (no irradiated) or irradiated by 3, 9, or 21 J (150; 450, or 1050 J/cm2). LP was performed in daily sessions for 3 days with a InGaAlP—660 nm (mean output: 50 mW, spot size: 2 mm2). Tumor volume was analyzed using (1) picrosirius staining to quantify collagen fibers content and (2) Verhoeff’s method to quantify blood vessels content. Tumor growth outcome measured in the 3-J group was not significantly different from controls. Nine and 21-J groups, presented significant and dose-dependent increases in tumor volume. Quantitative analysis of the intensity of collagen fibers and their organization in stroma and peri-tumoral microenvironment showed significant differences between irradiated and control group. Blood vessels count of 21-J group outnumbered the other groups. High doses (≥ 9 J) of LP showed a dose-dependent tumor growth, different collagen fibers characteristics, and eventually blood vessel growth, while a typical LLLT dose (3 J) appeared harmless on melanoma cell activity.

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References

  1. Chan HHL, Xiang L, Leung JCK, Tsang KWT, Lai K (2003) In vitro study examining the effect of sub-lethal QS 755 nm lasers on the expression of p16INK4a on melanoma cell lines. Lasers Surg Med 32:88–93

    Article  PubMed  Google Scholar 

  2. Kujawa J, Zavodnik IB, Lapshina A, Labieniec M, Bryszewska M (2004) Cell survival, DNA, and protein damage in B14 cells under low-intensity near-infrared (810 nm) laser irradiation. Photomed Laser Surg 22(6):504–508

    Article  PubMed  Google Scholar 

  3. Mognato M, Squizzato F, Facchin F, Zaghetto L, Corti L (2004) Cell growth modulation of human cells irradiated in vitro low-level laser therapy. Photomed Laser Surg 22(6):523–526

    Article  PubMed  Google Scholar 

  4. de Castro JL, Pinheiro AL, Werneck CE, Soares CP (2005) The effect of laser therapy on the proliferation of oral KB carcinoma cells: an in vitro study. Photomed Laser Surg 23(6):586–589

    Article  PubMed  Google Scholar 

  5. Sroka R, Schaffer M, Fuchs C, Pongratz T, Schrader-Reichard U, Busch M, Schaffer PM, Duhmke E, Baumgartner R (1999) Effects on the mitosis of normal and tumor cells induced by light treatment of different wavelengths. Lasers Surg Med 25(3):263–271

    Article  PubMed  CAS  Google Scholar 

  6. van Leeuwen RL, Dekker SK, Byers HR, Vermeer BJ, Grevelink JM (1996) Modulation of alpha 4 beta 1 and alpha 5 beta 1 integrin expression: heterogeneous effects of Q-switched Ruby, Nd:YAG, and Alexandrite lasers on melanoma cells in vitro. Lasers Surg Med 18(1):63–71

    Article  PubMed  Google Scholar 

  7. Zhu NW, Perks CM, Burd AR, Holly JM (1999) Changes in the levels of integrin and focal adhesion kinase (FAK) in human melanoma cells following 532 nm laser treatment. Int J Cancer 82(3):353–358

    Article  PubMed  CAS  Google Scholar 

  8. Marchesini R, Dasdia T, Melloni E, Rocca E (1989) Effect of low-energy laser irradiation on colony formation capability in different human tumor cells in vitro. Lasers Surg Med 9(1):59–62

    Article  PubMed  CAS  Google Scholar 

  9. Ocanã-Quero JM, Perez de la Lastra J, Gomez-Villamandos R, Moreno-Millan M (1998) Biological effect of helium-neon (He-Ne) laser irradiation on mouse myeloma (Sp2-Ag14) cell line in vitro. Lasers Med Sci 13:214–218

    Article  Google Scholar 

  10. Jamieson CW, Litwin MS, Longo SE, Krementz ET (1969) Enhancement of melanoma cell culture growth rate by ruby laser radiation. Life Sci 8(2):101–106

    Article  PubMed  CAS  Google Scholar 

  11. Abe M, Fujisawa K, Suzuki H, Sugimoto T, Kanno T (1993) Role of 830 nm low reactive level laser on the growth of an implanted glioma in mice. Keio J Med 42(4):177–179

    Article  PubMed  CAS  Google Scholar 

  12. Mester E, Lapis K, Tota JG (1971) Ultrastructural changes in Ehrlich ascites tumor cells following laser irradiation. Arch Geschwulstforsch 38(3):210–220

    PubMed  CAS  Google Scholar 

  13. Frigo L, Luppi JSS, Favero GM et al (2009) The effect of low-level laser irradiation (In-Ga-Al-AsP—660 nm) on melanoma in vitro and in vivo. BMC Cancer 9, article 404

  14. Lukashev ME, Werb ME (1998) ECM signalling: orchestrating cell behaviour and misbehaviour. Trends Cell Biol 8:437–441

    Article  PubMed  CAS  Google Scholar 

  15. Mettouchi A, Klein S, Guo W, Lopez-Lago M, Lemichez E, Westwick JK, Giancotti FG (2001) Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. Mol Cell 8:115–127

    Article  PubMed  CAS  Google Scholar 

  16. Zhao J, Pestell R, Guan JL (2001) Transcriptional activation of cyclin D1 promoter by FAK contributes to cell cycle progression. Mol Biol Cell 12:4066–4077

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Baron-Van Evercooren A, Kleinman HK, Seppä HE, Rentier B, Dubois-Dalcq M (1982) Fibronectin promotes rat Schwann cell growth and motility. J Cell Biol 93(1):211–216

    Article  PubMed  CAS  Google Scholar 

  18. Vitale M, Illario M, Di Matola T, Casamassima A, Fenzi G, Rossi G (1997) Integrin binding to immobilized collagen and fibronectin stimulates the proliferation of human thyroid cells in culture. Endocrinology 138(4):1642–1648

    Article  PubMed  CAS  Google Scholar 

  19. Mester E (1966) The use of the laser beam in therapy. Orv Hetil 107(22):1012–1016

    PubMed  CAS  Google Scholar 

  20. Medrado AR, Pugliese LS, Reis SR, Andrade ZA (2003) Influence of low level laser therapy on wound healing and its biological action upon myofibroblasts. Lasers Surg Med 32(3):239–244

    Article  PubMed  Google Scholar 

  21. Gavish L, Perez L, Gertz SD (2006) Low-level laser irradiation modulates matrix metalloproteinase activity and gene expression in porcine aortic smooth muscle cells. Lasers Surg Med 38(8):779–786

    Article  PubMed  Google Scholar 

  22. Choi SK, Kim JH, Lee D, Lee JB, Kim HM, Tchah HW, Hahn TW, Joo M, Ha CI (2008) Different epithelial cleavage planes produced by various epikeratomes in epithelial laser in situ keratomileusis. J Cataract Refract Surg 34(12):2079–2084

    Article  PubMed  Google Scholar 

  23. Chen CZ, Raghunath M (2009) Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis state of the art. Fibrogenesis Tissue Repair 2:7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Yamamoto Y, Kono T, Kotani H, Kasai S, Mito M (1996) Effect of low-power laser irradiation on procollagen synthesis in human fibroblasts. J Clin Laser Med Surg 14(3):129–132

    Article  PubMed  CAS  Google Scholar 

  25. Ferreira AN, Silveira L, Genovese WJ, de Araújo VC, Frigo L, de Mesquita RA, Guedes E (2006) Effect of GaAIAs laser on reactional dentinogenesis induction in human teeth. Photomed Laser Surg 24(3):358–365

    Article  PubMed  Google Scholar 

  26. Kikuchi T, Maemondo M, Narumi K, Matsumoto K, Nakamura T, Nukiwa T (2002) Tumor suppression induced by intratumor administration of adenovirus vector expressing NK4, a 4-kringle antagonist of hepatocyte growth factor, and naive dendritic cells. Blood 100(12):3950–3959

    Article  PubMed  CAS  Google Scholar 

  27. Kuwano H, Miyazaki T, Tsutsumi S, Hirayama I, Shimura T, Mochiki E, Nomoto K, Fukuchi M, Kato H, Asao T (2004) Cell density modulates the metastatic aggressiveness of a mouse colon cancer cell line, colon 26. Oncology 67(5–6):441–449

    Article  PubMed  Google Scholar 

  28. Rich L, Whittaker P (2005) Collagen and picrosirius red staining: a polarized light assessment of fibrillar hue and spatial distribution. Braz J Morphol Sci 22(2):97–104

    Google Scholar 

  29. Barbosa-Júnior AA (2001) Morphological computer-assisted quantitative estimation of stained fibrous tissue in liver sections: applications in diagnosis and experimental research. J Bras Patol 37(3):197–200

    Google Scholar 

  30. Coutinho EM et al (1997) Pathogenesis of schistosomal “pipestem” fibrosis (a low-protein diet inhibits the development of “pipestem” fibrosis in mice). Int J Exp Pathol 78:337–342

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Karu TI (1990) Effects of visible radiation on cultured cells. Photochem Photobiol 52:1089–1098

    Article  PubMed  CAS  Google Scholar 

  32. Liotta LA, Kohn EC (2001) The microenvironment of the tumour–host interface. Nature 411(6835):375–379

    Article  PubMed  CAS  Google Scholar 

  33. Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4(11):839–849

    Article  PubMed  CAS  Google Scholar 

  34. Tlsty TD, Coussens LM (2006) Tumor stroma and regulation of cancer development. Annu Rev Pathol 1:119–150

    Article  PubMed  CAS  Google Scholar 

  35. Pereira AN, Eduardo Cde P, Matson E, Marques MM (2002) Effect of low-power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts. Lasers Surg Med 31(4):263–267

    Article  PubMed  Google Scholar 

  36. Ignatieva N, Zakharkina O, Andreeva I, Sobol E, Kamensky V, Lunin V (2008) Effects of laser irradiation on collagen organization in chemically induced degenerative annulus fibrosus of lumbar intervertebral disc. Lasers Surg Med 40(6):422–432

    Article  PubMed  Google Scholar 

  37. Prockop D, Kivirikko KI (1995) Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem 64:403–434

    Article  PubMed  CAS  Google Scholar 

  38. Yu HS, Chang KL, Yu CL, Chen JW, Chen GS (1996) Low-energy helium-neon laser irradiation stimulates interleukin-1 alpha and interleukin-8 release from cultured human keratinocytes. J Investig Dermatol 107(4):593–596

    Article  PubMed  CAS  Google Scholar 

  39. Aimbire F, Albertini R, Pacheco MT et al (2006) Low-level laser therapy induces dose-dependent reduction of TNF-alpha levels in acute inflammation. Photomed Laser Surg 24:33–37

    Article  PubMed  CAS  Google Scholar 

  40. Herz DB, Aitken K, Bagli D (2003) Collagen directly stimulates bladder smooth muscle cell growth in vitro: regulation by extracellular regulated mitogen activated protein kinase. J Urol 170:2072–2076

    Article  PubMed  CAS  Google Scholar 

  41. Noël A, Jost M, Maquoi E (2008) Matrix metalloproteinases at cancer tumor–host interface. Semin Cell Dev Biol 19(1):52–60 Review

    Article  PubMed  CAS  Google Scholar 

  42. Koyama H, Raines EW, Bornfeldt KE, Roberts JM, Ross R (1996) Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. Cell 87:1069–1078

    Article  PubMed  CAS  Google Scholar 

  43. Bacakova L, Wilhel J, Herget J, Novotna J, Eckhart A (1997) Oxidized collagen stimulates proliferation of vascular smooth muscle cells. Exp Mol Pathol 64:185–194

    Article  PubMed  CAS  Google Scholar 

  44. Henriet P, Zhong ZD, Brooks PC, Weinberg KI, DeClerck YA (2000) Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1. Proc Natl Acad Sci U S A 97:10026–10031

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Hagendoorn J, Tong R, Fukumura D, Lin Q, Lobo J, Padera TP, Xu L, Kucherlapati R, Jain RK (2006) Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis. Cancer Res 66(7):3360–3364

    Article  PubMed  CAS  Google Scholar 

  46. Zhang W, Wu C, Pan W, Tian L, Xia J (2004) Low-power Helium-Neon laser irradiation enhances the expression of VEGF in murine myocardium. Chin Med J 117(10):1476–1480

    PubMed  CAS  Google Scholar 

  47. Ihsan FR (2005) Low-level laser therapy accelerates collateral circulation and enhances microcirculation. Photomed Laser Surg 23(3):289–294

    Article  PubMed  CAS  Google Scholar 

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Funding

Professor Lucio Frigo is thankful for the financial support of FAPESP (2007/59124-0).

Author information

Authors and Affiliations

  1. Biological Sciences and Health Center, Cruzeiro do Sul University, Av. Dr. Ussiel Cirilo, 225 São Miguel Paulista, São Paulo, SP, 08060-070, Brazil

    Lúcio Frigo, Joseli Maria Cordeiro & Denise Carvalho Roxo

  2. General Biology Department, State University of Ponta Grossa, Av. Gal. Carlos Cavalcanti, 4748, Ponta Grossa, PR, 84030-900, Brazil

    Giovani Marino Favero

  3. Laboratory of Biochemistry and Biophysics, Butantan Institute, Av. Dr. Vital Brasil, 1500, São Paulo, SP, 05599-000, Brazil

    Durnavei Augusto Maria

  4. Nove de Julho University (UNINOVE), Rua Vergueiro 235, São Paulo, SP, 01504-001, Brazil

    Ernesto Cesar Pinto Leal-Junior & Rodrigo Labat Marcos

  5. Institute for Physiotherapy, Bergen University College, Moellendalsvn 6, 5009, Bergen, Norway

    Jon Joensen & Jan Magnus Bjordal

  6. Physiotherapy Research Group, Department of Global and Public Health, University of Bergen, Kalfarveien 31, 5018, Bergen, Norway

    Jan Magnus Bjordal

  7. Biophotonics Applied in Health Sciences, Universidade Nove de Julho, Rua Vergueiro 235, São Paulo, SP, 01504-001, Brazil

    Rodrigo Labat Marcos

  8. Universidade do Vale do Paraíba, Av. Shishima Hifumi, 2911 - Urbanova, São José dos Campos, SP, 12244-000, Brazil

    Rodrigo Alvaro Brandão Lopes-Martins

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  1. Lúcio Frigo
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  2. Joseli Maria Cordeiro
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  4. Durnavei Augusto Maria
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  8. Denise Carvalho Roxo
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  9. Rodrigo Labat Marcos
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  10. Rodrigo Alvaro Brandão Lopes-Martins
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Correspondence to Rodrigo Labat Marcos.

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All experiments were carried out in accordance with the guidelines from Cruzeiro do Sul University Bioethical Council for human and animal care, PROTOCOL 011/07.

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The authors declare that they have no conflict of interest.

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Professor Ernesto Cesar Pinto Leal-Junior received research support from Multi Radiance Medical (Solon, OH), a laser device manufacturer.

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Frigo, L., Cordeiro, J.M., Favero, G.M. et al. High doses of laser phototherapy can increase proliferation in melanoma stromal connective tissue. Lasers Med Sci 33, 1215–1223 (2018). https://doi.org/10.1007/s10103-018-2461-5

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  • DOI: https://doi.org/10.1007/s10103-018-2461-5

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