Side Population Cell Level in Human Breast Cancer and Factors Related to Disease-free Survival

Jin, Chunlei; Zou, Tong; Li, J.; Chen, X.Q.; Liu, X.; Wang, Y.Y.; Wang, X.; Che, Yi-Qun; Wang, X.C.; Sriplung, Hutcha

doi:10.7314/apjcp.2015.16.3.991

Cited by 7 publications

(8 citation statements)

References 38 publications

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“…Moreover, the more malignant the tumor phenotype, the higher the proportion of SP cells found 10,38–41 . The proportion of SP cells in and of itself, or genes that are overexpressed in the SP cells, are also reported as independent poor prognostic factors 11,42,43 . Because repression of the six individual genes increased the SP as we have demonstrated, and because ovarian cancer is characterized by marked chromosomal instability 44 , ovarian cancer may easily enhance the malignant phenotype during progression or relapse via a genetic change that increases the fraction of SP cells.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that SP cells are chemoresistant, have sphere forming capacity, exhibit single cell clonogenicity, and in vivo tumorigenicity 8,9 . In addition, in ovarian cancer, a relatively high proportion of SP cells are found in samples from clinical relapse 10 , and the proportion of SP cells is said to be an independent factor for poor prognosis 11 . However, little is known about the factor(s) that regulate the proportion of SP cells in cancer.…”

Section: Introductionmentioning

confidence: 99%

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Acquisition of a side population fraction augments malignant phenotype in ovarian cancer

Yamanoi

Baba

Abiko

et al. 2019

Sci Rep

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Side population (SP) cells harbor malignant phenotypes in cancer. The aim of this study was to identify genes that modulate the proportion of ovarian cancer SP cells. Using a shRNA library targeting 15,000 genes, a functional genomics screen was performed to identify genes whose suppression increased the SP percentage. The biological effects caused by alteration of those identified genes were investigated in vitro and in vivo. We found that suppression of MSL3, ZNF691, VPS45, ITGB3BP, TLE2, and ZNF498 increased the proportion of SP cells. Newly generated SP cells exhibit greater capacity for sphere formation, single cell clonogenicity, and in vivo tumorigenicity. On the contrary, overexpression of MSL3, VPS45, ITGB3BP, TLE2, and ZNF498 decreased the proportion of SP cells, sphere formation capacity and single cell clonogenicity. In ovarian cancer cases, low expression of MSL3, ZNF691 and VPS45 was related to poor prognosis. Suppression of these six genes enhanced activity of the hedgehog pathway. Cyclopamine, a hedgehog pathway inhibitor, significantly decreased the number of SP cells and their sphere forming ability. Our results provide new information regarding molecular mechanisms favoring SP cells and suggest that Hedgehog signaling may provide a viable target for ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acquisition of a side population fraction augments malignant phenotype in ovarian cancer

Yamanoi

Baba

Abiko

et al. 2019

Sci Rep

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“…Our data suggest that the expression of stem cell genes could be related to the progression of the disease, as SP cells from the last stages of the disease, such as PCL, exhibited overexpression of a higher number of stem cell metabolism genes compared to MM plasma cells and MGUS plasma cells. The percentage of SP could also be related to disease progression, as PCL SP cells represent 50% of tumor cells [ 34 ]. This finding supports the SP representing the stem compartment.…”

Section: Discussionmentioning

confidence: 99%

Natural killer cells efficiently target multiple myeloma clonogenic tumor cells

Leivas

Risueño

Guzmán

et al. 2021

Cancer Immunol Immunother

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The multiple myeloma (MM) landscape has changed in the last few years, but most patients eventually relapse because current treatment modalities do not target clonogenic stem cells, which are drug-resistant and can self-renew. We hypothesized that side population (SP) cells represent myeloma clonogenic stem cells and, searching for new treatment strategies, analyzed the anti-myeloma activity of natural killer (NK) cells against clonogenic cells. Activated and expanded NK cells (NKAE) products were obtained by co-culturing NK cells from MM patients with K562-mb15-41BBL cell line and characterized by flow cytometry. Functional experiments against MM cells were performed by Eu-TDA release assays and methylcellulose clonogenic assays. Side population was detected by Dye Cycle Violet labeling and then characterized by flow cytometry and RNA-Seq. Self-renewal capacity was tested by clonogenic assays. Sorting of both kind of cells was performed for time-lapse microscopy experiments. SP cells exhibited self-renewal potential and overexpressed genes involved in stem cell metabolism. NK cells from MM patients exhibited dysregulation and had lower anti-tumor potential against clonogenic cells than healthy donors’ NK cells. Patients’ NK cells were activated and expanded. These cells recovered cytotoxic activity and could specifically destroy clonogenic myeloma cells. They also had a highly cytotoxic phenotype expressing NKG2D receptor. Blocking NKG2D receptor decreased NK cell activity against clonogenic myeloma cells, and activated NK cells were able to destroy SP cells, which expressed NKG2D ligands. SP cells could represent the stem cell compartment in MM. This is the first report describing NK cell activity against myeloma clonogenic cells.

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“…Chemotherapy and radiotherapy have emerged as the most common modalities of cancer treatment. [ 1 ] Cisplatin (Cis) is one of the most important chemotherapeutic drugs used in the treatment of a wide range of solid tumors. [ 2 ] It was found to have anti-tumor effects in animal models,[ 3 ] but its use is often associated with a number of side effects such as nephrotoxicity, peripheral neuropathy, ototoxicity, gastrointestinal disorder, and myelosuppression.…”

Section: Introductionmentioning

confidence: 99%

Ameliorative effects of chloroform fraction of Cocos nucifera L. husk fiber against Cisplatin-induced toxicity in rats

2016

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Background:Cisplatin (Cis) is used in the treatment of solid tumors and is known to elicit serious side effects.Objective:The present study investigated the protective effects of chloroform fraction of Cocos nucifera husk fiber (CFCN) against Cis-induced organs’ damage and chromosomal defect in rats. Quercetin (QUE), standard antioxidant, served as positive control.Materials and Methods:Thirty male Wistar rats were assigned into six groups and treated with corn oil (control), Cis alone, Cis + CFCN, CFCN alone, Cis + QUE, and QUE alone. QUE and CFCN were given at 50 and 200 mg/kg/day, respectively, by oral gavage for 7 days before the rats were exposed to a single dose of Cis (10 mg/kg, intraperitoneal) at the last 36 h of study.Results:Administration of Cis alone caused a significant (P < 0.05) increase in the levels of serum creatinine and urea by 72% and 70%, respectively, when compared with the control. The activity of serum aspartate aminotransferase was significantly (P < 0.05) increased while alanine aminotransferase and alkaline phosphatase were insignificantly (P > 0.05) affected in Cis-treated rats. Furthermore, the activities of hepatic and renal catalase, superoxide dismutase, glutathione S-transferase, glutathione peroxidase, and levels of reduced glutathione were significantly (P < 0.05) decreased in Cis-treated rats with concomitant elevation of malondialdehyde. Cis exposure increased the frequency of micro nucleated polychromatic erythrocytes (mPCE) by 92%. Pretreatment with CFCN inhibited lipid peroxidation, enhanced the activities of some antioxidative enzymes and reduced the frequency of mPCE.Conclusions:Chloroform fraction of CFCN may protect against organs damage by Cis. Further studies are required to determine the component of the plant responsible for this activity.SUMMARY Cisplatin (Cis) is used in the treatment of solid tumors and is known to elicit serious side effects. This study investigated the protective effects of chloroform fraction of Cocos nucifera husk fiber (CFCN) against Cis-induced organs’ damage while quercetin (QUE) served as standard antioxidant.Thirty male Wistar rats were assigned into six groups and treated with corn oil (Control), Cis alone, Cis + CFCN, CFCN alone, Cis + QUE and QUE alone.QUE and CFCN were given at 50 and 200 mg/kg/day respectively by oral gavage for seven days before the rats were exposed to a single dose of Cis (10mg/kg, i.p.) at the last 36 h of study. Results indicate that administration of Cis caused a significant (P<0.05) increase in the levels of serum creatinine and urea by 72% and 70% respectively.The activity of serum aspartate aminotransferase was significantly (P <0.05) increased while alanine aminotransferase and alkaline phosphatase were insignificantly (P>0.05) affected in Cis-treated rats.The activities of hepatic and renal catalase, superoxide dismutase, glutathione-s-transferase, glutathione peroxidase and levels of reduced glutathione were significantly (P<0.05) decreased in Cis-treated rats with concomitant elevation of malondialdeh...

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Side Population Cell Level in Human Breast Cancer and Factors Related to Disease-free Survival

Cited by 7 publications

References 38 publications

Acquisition of a side population fraction augments malignant phenotype in ovarian cancer

Acquisition of a side population fraction augments malignant phenotype in ovarian cancer

Natural killer cells efficiently target multiple myeloma clonogenic tumor cells

Ameliorative effects of chloroform fraction of Cocos nucifera L. husk fiber against Cisplatin-induced toxicity in rats

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