Functional significance of CD105-positive cells in papillary renal cell carcinoma

Matak, Damian; Brodaczewska, Klaudia; Szczylik, Cezary; Koch, Irena; Myszczyszyn, Adam; Lipiec, Monika; Lewicki, Sławomir; Szymański, Łukasz; Zdanowski, Robert; Czarnecka, Anna M.

doi:10.1186/s12885-016-2985-7

Cited by 15 publications

(14 citation statements)

References 79 publications

(70 reference statements)

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“…In order to investigate the effect of WIN-55 treatment on RCC cells ability to form 3D spheres/colonies, cells were cultured and harvested as described above and washed twice with PBS to remove any FBS present in cell culture media. Cells were counted and seeded at density of 100 cells/well in ultra-low attachment 96 wells plates (TC plate, suspension, F, Sarstetd, Numbrecht, Germany) supplemented with sphere promoting media as described previously [ 28 ]. Later WIN-55 (0 μM (control), subtoxic concentration (10 μM) prepared in sphere promoting media) was added in wells with cells in the beginning (day 0), at the moment when cells started to form spheres (day 2–3) and at the end when spheres were formed (day 6–7).…”

Section: Methodsmentioning

confidence: 99%

Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212–2 in renal cell carcinoma

et al. 2018

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BackgroundThe anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB1 and CB2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212–2 (WIN-55)] in RCC cell lines.MethodsHuman RCC cell lines were used for this study. The CB1 and CB2 gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB1 and CB2 receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB1 and CB2 receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells.ResultsThe CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB2 receptor as compared to CB1 in RCC cells. Immunocytochemical staining also confirmed the expression of the CB1 and CB2 proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB2 agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis.ConclusionsThis study elucidated the involvement of CB2 in the in vitro inhibition of RCC cells, and future applications of CB2 agonists in the prevention and management of RCC are discussed.

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Section: Methodsmentioning

confidence: 99%

Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212–2 in renal cell carcinoma

et al. 2018

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“…Cloning with a diameter not less than 60 μm is considered a clone. Survival fraction curves were determined as previously described [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Dihydroartemisinin induces autophagy-dependent death in human tongue squamous cell carcinoma cells through DNA double-strand break-mediated oxidative stress

Shi

Wang

et al. 2017

Oncotarget

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Dihydroartemisinin is an effective antimalarial agent with multiple biological activities. In the present investigation, we elucidated its therapeutic potential and working mechanism on human tongue squamous cell carcinoma (TSCC). It was demonstrated that dihydroartemisinin could significantly inhibit cell growth in a dose- and time-dependent manner by the Cell Counting Kit-8 and colony formation assay in vitro. Meanwhile, autophagy was promoted in the Cal-27 cells treated by dihydroartemisinin, evidenced by increased LC3B-II level, increased autophagosome formation, and increased Beclin-1 level compared to dihydroartemisinin-untreated cells. Importantly, dihydroartemisinin caused DNA double-strand break with simultaneously increased γH2AX foci and oxidative stress; this inhibited the nuclear localization of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), finally leading to autophagic cell death. Furthermore, the antitumor effect of dihydroartemisinin-monotherapy was confirmed with a mouse xenograft model, and no kidney injury associated with toxic effect was observed after intraperitoneal injection with dihydroartemisinin for 3 weeks in vivo. In the present study, it was revealed that dihydroartemisinin-induced DNA double-strand break promoted oxidative stress, which decreased p-STAT3 (Tyr705) nuclear localization, and successively increased autophagic cell death in the Cal-27 cells. Thus, dihydroartemisinin alone may represent an effective and safe therapeutic agent for human TSCC.

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“…CD105 silencing accelerate senescence in vitro and significantly decreased tumorigenicity and gemcitabine resistance 28 . Nevertheless, CD105 expression seems to be related with stemness in ccRCC, but not other subtypes of RCC 20,35 and RCC cell lines based results must be interpreted in relation to their pathology (subtype) and origin 9 .…”

Section: Discussionmentioning

confidence: 90%

“…tumor sphere formation and staining with stem-like (cSc) markers. RCC cells were counted and seeded at density of 100 cells/well in ultra-low attachment 24 wells plates (TC plate, suspension, F, Sarstetd, Numbrecht, Germany) supplemented with sphere promoting media as described previously 20,77 . Later culture media was removed, and tumor spheres were rinsed briefly in PBS (3 times).…”

Section: Resultsmentioning

confidence: 99%

“…In order to analyze appropriate RCC subtype specific cell lines must be selected based on their confirmed histology 9 . Data on the expression of markers should be interpreted along with the origin of RCC cells including tumor type and site of origin 8,20 . For initial characterization of RCC-CSCs candidates preselected cell surface were used and cells were isolated including CD105+ cells 13 and CD133+ cells 15 from nephrectomy specimens (primary tumor); CD44+ (ALDH1+) cells -from 293T human embryonic kidney cell line 10,11 ; CXCR4+ cells from RCC-26, RCC-53 cell lines 17 .…”

Section: Discussionmentioning

confidence: 99%

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Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

Fiedorowicz

Khan

Strzemecki

et al. 2020

Sci Rep

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clear cell renal cell carcinoma (ccRcc) is the most common kidney cancer. prognosis for ccRcc is generally poor since it is largely resistant to chemo-and radiotherapy. Many studies suggested that cancer stem cells/tumor initiating cells (CSCs/TICs) are responsible for development of tumor, disease progression, aggressiveness, metastasis and drug resistance. However, tumorigenic potential of CSCs/ tics isolated from established Rcc cell lines-basic ccRcc research model-has never been investigated in vivo. CD105+, CD105−, CD44+ and CD44− as well as CD44−/CD105− CD44+/CD105+ and CD44−/ CD105+ cells were isolated from Caki-1 RCC cell line, confirming coexistence of multiple subpopulations of stem-related phenotype in stable cell line. Sorted cells were injected subcutaneously into noD SciD mice and tumor growth was monitored with MRi and pet/ct. tumor growth was observed after implantation of CD105+, CD44+, CD44−, CD44−/CD105+ and CD44−/CD105− but not CD105− or CD44+/CD105+. Implantation of CD44−/CD105− cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors. All the tumors were characterized by low uptake of [18F]FDG. CD105+ and CD44− tumors expresses Nanog and Oct-4, while CD44− tumors additionally expressed endothelial cell marker-CD31. Renal cell carcinoma (RCC), is the 10th malignancy worldwide and the most frequent type of kidney cancer in adults. Each year in Europe approximately 88 400 patients are diagnosed with RCC; the incidence and mortality of RCC are rising at a rate of 2-3% per decade, therefore novel therapies directed against RCC are needed. At the same time despite advancements in diagnostic techniques, up to 30% of newly diagnosed patients already present with metastases, and a large portion of patients that undergo surgical treatment experience the RCC recurrence, therefore drugs targeted against metastasis initiating cells would be of great interest in the future 1,2. Cancer stem cells (CSCs) are characterized by the potential to self-renew, high tumorigenicity in nude mice and the ability to efficiently reconstitute all tumor subpopulations and primary tumor phenotype 3-5. CSCs are also responsible not only for cancer development, but also for disease recurrence, progression and metastatic spread, together with cancer aggressiveness, including treatment resistance such as chemo/radiotherapy, and targeted treatment 6,7 , therefore basic research with careful model selection to understand their biology is mandatory to define novel potential therapeutic targets for all RCC subtypes 8,9 .

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Functional significance of CD105-positive cells in papillary renal cell carcinoma

Cited by 15 publications

References 79 publications

Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212–2 in renal cell carcinoma

Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212–2 in renal cell carcinoma

Dihydroartemisinin induces autophagy-dependent death in human tongue squamous cell carcinoma cells through DNA double-strand break-mediated oxidative stress

Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

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