mTHPC‐Mediated Photodynamic Therapy is Effective in the Metastatic Human 143B Osteosarcoma Cells

Reidy, Kerstin; Campanile, Carmen; Muff, Roman; Born, Walter; Fuchs, Bruno

doi:10.1111/j.1751-1097.2012.01096.x

Cited by 21 publications

(25 citation statements)

References 32 publications

(44 reference statements)

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“…Murine osteosarcoma cell line DLM‐8 was obtained from the Chinese Academy of Science, Human osteosarcoma cell lines 143B, HOS, SaoS2 and U2OS were obtained from American Type Culture Collection (ATCC). 143B and HOS originate from the same host while 143B is highly metastatic compared with HOS . U2OS is wild‐type p53 while SaoS2 is a null p53 cell line .…”

Section: Methodsmentioning

confidence: 99%

Hiporfin‐Mediated Photodynamic Therapy in Preclinical Treatment of Osteosarcoma

Sun

Zhou

Zeng

et al. 2015

Photochem & Photobiology

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This study was carried out to investigate the anti-tumor effect and mechanism of hiporfin-mediated photodynamic therapy (hiporfin-PDT) in osteosarcoma. We found that hiporfin accumulated mainly in the cytoplasm of osteosarcoma cells in a time and concentration-dependent manner. Hiporfin-PDT inhibited the proliferation, induced apoptosis and produced cell cycle arrest at G2M in osteosarcoma cell lines. Hiporfin-PDT increased the expression of cleaved-caspase-3, cleaved PARP-1, Bax and RIP1 while it decreased the expression of Bcl-2; in addition, low concentration of hiporfin increased LC3 conversion. Furthermore, cell death caused by hiporfin-PDT could be rescued by Nec-1 but not by Z-VAD-FMK. Production of reactive oxygen species was increased after hiporfin-PDT. In vivo studies showed a significant decrease in tumor volume and weight after hiporfin-PDT in all three tumor mouse models investigated (subcutaneous and orthotopic). Histological analysis showed widespread cell apoptosis and necrosis after treatment. Immunohistochemistry also showed upregulation of cleaved-caspase-3 and downregulation of Bcl-2 after hiporfin-PDT. These results indicate that hiporfin-PDT exhibits a killing effect in osteosarcoma both in vitro and in vivo, which is associated with apoptosis and necroptosis, while autophagy plays a protective role. All these findings shed light on a potential future clinical use for hiporfin in the treatment of osteosarcoma.

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Section: Methodsmentioning

confidence: 99%

Hiporfin‐Mediated Photodynamic Therapy in Preclinical Treatment of Osteosarcoma

Sun

Zhou

Zeng

et al. 2015

Photochem & Photobiology

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“…The cells were cultured in DMEM (4.5 g/l glucose)/HamF12 (1∶1) medium (Invitrogen; Carlsbad, CA), supplemented with 10% heat-inactivated FCS (GIBCO, Basel, Switzerland), at 37°C in a humidified atmosphere of 5% CO 2 /95% air. CD44 expression was stably silenced by retroviral expression of shRNA in 143-B cells that were transduced with a LacZ gene for tumor cell identification by X-gal staining in mouse tissues [21]. Retroviral constructs in the pSirenRetroQ vector (Clontech; Paolo Alto, CA) coding for CD44 transcript-targeting shRNA (shCD44) and for non-targeting control shRNA (Ctrl shRNA) were kindly provided by Prof. Ivan Stamenkovic (Lausanne, Switzerland) [22].…”

Section: Methodsmentioning

confidence: 99%

Silencing of CD44 Gene Expression in Human 143-B Osteosarcoma Cells Promotes Metastasis of Intratibial Tumors in SCID Mice

et al. 2013

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Osteosarcoma (OS) is the most frequent primary malignant bone cancer in children and adolescents with a high propensity for lung metastasis. Therefore, it is of great importance to identify molecular markers leading to increased metastatic potential in order to devise more effective therapeutic strategies that suppress metastasis, the major cause of death in OS. CD44, the principal receptor for the extracellular matrix component hyaluronan (HA), is frequently found overexpressed in tumor cells and has been implicated in metastatic spread in various cancer types. Here, we investigated the effects of stable shRNA-mediated silencing of CD44 gene products on in vitro and in vivo metastatic properties of the highly metastatic human 143-B OS cell line. In vitro, CD44 knockdown resulted in a 73% decrease in the adhesion to HA, a 57% decrease in the migration rate in a trans-filter migration assay, and a 28% decrease in the cells' capacity for anchorage-independent growth in soft agar compared to the control cells, implicating that CD44 expression contributes to the metastatic activity of 143-B cells. However, making use of an orthotopic xenograft OS mouse model, we demonstrated that reduced CD44 expression facilitated primary tumor growth and formation of pulmonary metastases. The enhanced malignant phenotype was associated with decreased adhesion to HA and reduced expression of the tumor suppressor merlin in vivo. In conclusion, our study identified CD44 as a metastasis suppressor in this particular experimental OS model.

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“…Here, we describe the procedures to quantify the uptake of this liposomal formulation, and to perform PDT in two human OS cell lines; the low metastatic HOS and the high metastatic 143B cells. Some of the data presented here have been reported earlier 11 . The approach described here enables us to study the effect of a metastatic phenotype on PDT efficacy.…”

Section: Introductionmentioning

confidence: 65%

“…We also would like to thank Kerstin Reidy, who generated a large part of the results and was coresponsible for its publication 11 . This work was supported by grants from the Schweizerischer Verein Balgrist, the University of Zurich, the Krebsliga Zurich as well as by a grant from the Walter L. and Johanna Wolf Foundation, Zurich, Switzerland and a grant from EuroNanoMed ERA-NET ⁄SNF Swiss National Science Foundation 31NM30-131004 ⁄ 1.…”

Section: Acknowledgementsmentioning

confidence: 99%

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells <em>In Vitro</em>

Meier

Campanile

Botter

et al. 2014

JoVE

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In recent years, there has been the difficulty in finding more effective therapies against cancer with less systemic side effects. Therefore Photodynamic Therapy is a novel approach for a more tumor selective treatment.Photodynamic Therapy (PDT) that makes use of a nontoxic photosensitizer (PS), which, upon activation with light of a specific wavelength in the presence of oxygen, generates oxygen radicals that elicit a cytotoxic response 1 . Despite its approval almost twenty years ago by the FDA, PDT is nowadays only used to treat a limited number of cancer types (skin, bladder) and nononcological diseases (psoriasis, actinic keratosis) 2 .The major advantage of the use of PDT is the ability to perform a local treatment, which prevents systemic side effects. Moreover, it allows the treatment of tumors at delicate sites (e.g. around nerves or blood vessels). Here, an intraoperative application of PDT is considered in osteosarcoma (OS), a tumor of the bone, to target primary tumor satellites left behind in tumor surrounding tissue after surgical tumor resection. The treatment aims at decreasing the number of recurrences and at reducing the risk for (postoperative) metastasis.In the present study, we present in vitro PDT procedures to establish the optimal PDT settings for effective treatment of widely used OS cell lines that are used to reproduce the human disease in well established intratibial OS mouse models. The uptake of the PS mTHPC was examined with a spectrophotometer and phototoxicity was provoked with laser light excitation of mTHPC at 652 nm to induce cell death assessed with a WST-1 assay and by the counting of surviving cells. The established techniques enable us to define the optimal PDT settings for future studies in animal models. They are an easy and quick tool for the evaluation of the efficacy of PDT in vitro before an application in vivo.

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mTHPC‐Mediated Photodynamic Therapy is Effective in the Metastatic Human 143B Osteosarcoma Cells

Cited by 21 publications

References 32 publications

Hiporfin‐Mediated Photodynamic Therapy in Preclinical Treatment of Osteosarcoma

Hiporfin‐Mediated Photodynamic Therapy in Preclinical Treatment of Osteosarcoma

Silencing of CD44 Gene Expression in Human 143-B Osteosarcoma Cells Promotes Metastasis of Intratibial Tumors in SCID Mice

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells <em>In Vitro</em>

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