Reversal of the Migratory and Invasive Phenotype of Ras‐Transfected Mammary Cells by Photodynamic Therapy Treatment

• Published in: Journal of cellular biochemistry 2017-03, Vol.118 (3), p.464-477
• Main Authors: Calvo, Gustavo, Sáenz, Daniel, Simian, Marina, Sampayo, Rocío, Mamone, Leandro, Vallecorsa, Pablo, Batlle, Alcira, Casas, Adriana, Di Venosa, Gabriela
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Transformed; Female; Genes, ras; Humans; INVASION; Mammary Glands, Human - metabolism; Mammary Glands, Human - pathology; METASTASIS; MIGRATION; PDT; Photochemotherapy - methods; PHOTODYNAMIC THERAPY; Photosensitizing Agents - pharmacology; RAS ONCOGENE; Transfection
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25657

ABSTRACT Photodynamic therapy (PDT) is a non‐thermal technique for inducing tumor damage following administration of a light‐activated photosensitizing drug (PS). In a previous work we found that PDT induces cytoskeleton changes in HB4a‐Ras cells (human mammary breast carcinoma HB4a cells transfected with the RAS oncogene). In the present work we have studied the migratory and invasive features and the expression of proteins related to these processes on HB4a‐Ras cells after three successive cycles of PDT using different PSs: 5‐aminolevulinic acid (ALA), Verteporfin (Verte), m‐tetrahydroxyphenylchlorin (m‐THPC), and Merocyanine 540 (MC). A slight (1.25‐ to 2‐fold) degree of resistance was acquired in cell populations subjected to the three successive PDT treatments. However, complete cell killing was achieved after a light dose increase. Regardless of the PS employed, all the PDT‐treated populations had shorter stress fibres than the untreated control HB4a‐Ras cells, and the number of dorsal stress fibres was decreased in the PDT‐treated populations. E‐Cadherin distribution, which was already aberrant in HB4a‐Ras cells, became even more diffuse in the PDT‐treated populations, though its expression was increased in some of them. The strong migratory and invasive ability of HB4a‐Ras cells in vitro was impaired in all the PDT‐treated populations, with a behavior that was similar to the parental non‐tumoral HB4a cells. MMP‐2 and ‐9 metalloproteinase activities were also impaired in the PDT‐treated populations. The evidence presented herein suggests that the cells surviving PDT would be less metastatic than the initial population. These findings encourage the use of PDT in combination with other treatments such as intraoperative or post‐surgery therapeutic procedures. J. Cell. Biochem. 118: 464–477, 2017. © 2016 Wiley Periodicals, Inc. Mammary tumor HB4a transfected with the Ras oncogene (HB4a‐Ras) were treated with 3 sucessive cycles of Photodynamic Therapy (PDT) using different photosensitizing drugs (ALA, Verte, MC, and m‐THPC). The strong migratory and invasive ability of HB4a‐Ras cells in vitro was dramatically impaired in all the PDT treated populations, thus resembling the parental non‐tumoral HB4a normal cells. The evidence presented in this work suggests that PDT would impact negatively on the in vivo metastasis. This encourages the use of photodynamic treatment in combination with other treatments such as in intraoperative procedures or post‐surgery.