Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines

Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Axcrona, Karol; Kvalheim, Gunnar; Giercksky, Karl Erik; Nesland, Jahn M.; Suo, Zhenhe

doi:10.1007/s13277-012-0325-3

Cited by 27 publications

(24 citation statements)

References 42 publications

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“…PC‐3 cells were grown at low cell density (200 cells/well) in the absence or presence of the indicated concentration of celecoxib (10–100 μmol/L) for 14 days. PC‐3 cells formed colonies, as described by others . Long‐term celecoxib treatment inhibited anchorage‐dependent colony formation in a concentration‐dependent manner (Fig.…”

Section: Resultssupporting

confidence: 82%

Cyclooxygenase‐2 inhibitor suppresses tumour progression of prostate cancer bone metastases in nude mice

et al. 2014

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Objective• To assess whether celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor with anti-cancer properties, has an inhibitory effect on tumour establishment and progression of prostate cancer (PCa) bone metastases. Materials and Methods• PC-3 stable luciferase-expressing cells were injected into male nude mice by intracardiac (i.c.) and intratibial (i.t.) injections, and the effect of celecoxib on bone metastases was then recorded using bioluminescence image analysis.• In cases of chemoprevention, mice received 3 mg/kg celecoxib from 1 week before cell implantation until the end of the study, and to test the therapeutic effect, mice received celecoxib 1 week after cell implantation until the end of the study.• Tumour tissue samples were histologically examined and COX-2 expression was quantified at the protein level. Results• Celecoxib significantly decreased cell viability and the proliferation of human PCa cells in vitro in a dose-dependent manner.• Bone metastases were detected after i.c. injection in nude mice.• Celecoxib (15 ppm) administered before i.c. injection did not inhibit the cellular metastatic potential, as the numbers of bone metastases were similar in both groups. However, celecoxib did decrease metastatic progression in the osseous environment when cells were injected directly into the tibia (P < 0.05).• At the protein level, COX-2 expression was significantly decreased in the celecoxib treatment group (P < 0.01). Conclusion• In a preclinical mice model, celecoxib administered orally at the standard human dose inhibits the progression of established PCa bone metastases.

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Section: Resultssupporting

confidence: 82%

Cyclooxygenase‐2 inhibitor suppresses tumour progression of prostate cancer bone metastases in nude mice

et al. 2014

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“…Consistent with comparisons to the polystyrene-supported metastatic niche, elevations in uPA, SCF, osteopontin, VEGF-A, secreted VEGF receptor (sVEGFR)-2 and IL-6 were observed in the hydrogel-supported metastatic niche compared to the baseline values. Distinctively, promoters of dormancy were also increased – b-FGF can be a direct inducer of dormancy 39 and while SCF is a cancer biomarker, it is also involved in dormant stem cells maintenance 40, 41 . Integration of the MDA-MB-231 cells may have been enhanced by the increased levels of osteopontin, which has been shown previously to significantly enhance heterotypic interactions with hepatocytes in CRC metastasis to liver 42 .…”

Section: Resultsmentioning

confidence: 99%

A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties

et al. 2017

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Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming ‘cure’ of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells. However, we observed that the dormant cells were localized primarily within the 3D tissue, while the proliferative cells were in contact with the polystyrene scaffold. As matrix stiffness is known to drive inflammatory and malignant behaviors, we explored the occurrence of spontaneous tumor dormancy and inflammatory phenotype. The microphysiological system was retrofitted with PEGDa-SynKRGD hydrogel scaffolding, which is softer and differs in the interface with the tissue. The microphysiological system incorporated donor-matched primary human hepatocytes and non-parenchymal cells (NPCs), with MDA-MB-231 breast cancer cells. Hepatic tissue in hydrogel scaffolds secreted lower levels of pro-inflammatory analytes, and was more responsive to inflammatory stimuli. The proportion of tumor cells entering dormancy was markedly increased in the hydrogel-supported tissue compared to polystyrene. Interestingly, an unexpected differential response of dormant cells to varying chemotherapeutic doses was identified, which if reflective of patient pathophysiology, has important implications for patient dosing regimens. These findings highlight the metastatic microphysiological system fitted with hydrogel scaffolds as a critical tool in the assessment and development of therapeutic strategies to target dormant metastatic breast cancer.

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“…[3, 4, 13, 17, 18] To determine whether CD117 expression in primary tumors was associated with the levels of its ligand stem cell factor (SCF), we stained sections from high and low-grade patients for CD117 and SCF (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

“…[23] SCF in the circulation or bone marrow [24] may serve as a chemotactic factor [23] stimulating the mobilization of CD117 + cells into the circulation. Further, exogenous SCF treatment promotes expression of CD117 by prostate cancer cells, in addition to the stem cell factors Oct3/4 and Nanog, [17] indicating that a stem cell like phenotype may be induced by CD117 activation by SCF.…”

Section: Discussionmentioning

confidence: 99%

CD117+ cells in the circulation are predictive of advanced prostate cancer

et al. 2014

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Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metastasis. However, the frequency and predictive value of CTCs in patients remains unknown. If circulating cells are involved in tumor aggressiveness and metastasis, then cell levels should decline upon tumor removal in localized cancer patients, but remain high in metastatic patients. Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34-positive cell percentages in the blood of patients undergoing radical prostatectomy for localized cancer were assessed by flow cytometry prior to intervention and 1–3 months postoperatively. Only circulating CD117+ cell percentages decreased after radical prostatectomy, increased with cancer progression and correlated with high PSA values. Notably, postoperative CD117+ levels did not decrease in patients experiencing biochemical recurrence. In a xenograft model, CD117-enriched tumors were more vascularized and aggressive. Thus, CD117 expression on CTCs promotes tumor progression and could be a biomarker for prostate cancer diagnosis, prognosis, and/or response to therapy.

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Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines

Cited by 27 publications

References 42 publications

Cyclooxygenase‐2 inhibitor suppresses tumour progression of prostate cancer bone metastases in nude mice

Cyclooxygenase‐2 inhibitor suppresses tumour progression of prostate cancer bone metastases in nude mice

A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties

CD117+ cells in the circulation are predictive of advanced prostate cancer

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