Effect of adipocyte-secreted factors on EpCAM+/CD133+ hepatic stem cell population

Karagonlar, Zeynep Fırtına; Koç, Doğukan; Şahin, Erdem; Avcı, Sanem Tercan; Yılmaz, M.; Atabey, Neşe; Erdal, Esra

doi:10.1016/j.bbrc.2016.04.137

Cited by 12 publications

(9 citation statements)

References 39 publications

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“…In order to isolate the LCSCs (EpCAM + /CD133 + ) and non-stem cells (EpCAM − /CD133 − ) from the HuH7 cell line, cells were stained with EpCAM-FITC (#130-110-998, Miltenyi Biotech, Auburn, AL, USA) and CD133-APC (#130-111-000, Miltenyi Biotech, Auburn, AL, USA) antibodies, and sorted using BD FACS Aria III cell sorter. Cells were cultured as previously described [45].…”

Section: Isolation Of Lcscs and Non-stem Cells From Huh-7mentioning

confidence: 99%

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM−/CD133− nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7

Karagonlar

Akbari

Karabicici

et al. 2020

Cells

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The complex and heterogeneous nature of hepatocellular carcinoma (HCC) hampers the identification of effective therapeutic strategies. Cancer stem cells (CSCs) represent a fraction of cells within tumors with the ability to self-renew and differentiate, and thus significantly contribute to the formation and maintenance of heterogeneous tumor mass. Increasing evidence indicates high plasticity in tumor cells, suggesting that non-CSCs could acquire stem cell properties through de-differentiation or reprogramming processes. In this paper, we reveal KLF4 as a transcription factor that can induce a CSC-like phenotype in non-CSCs through upregulating the EpCAM and E-CAD expression. Our studies indicated that KLF4 could directly bind to the promoter of EpCAM and increase the number of EpCAM+/CD133+ liver cancer stem cells (LCSCs) in the HuH7 HCC cell line. When KLF4 was overexpressed in EpCAM−/CD133− non-stem cells, the expressions of hepatic stem/progenitor cell genes such as CK19, EpCAM and LGR5 were significantly increased. KLF4 overexpressing non-stem cells exhibited greater cell viability upon sorafenib treatment, while the cell migration and invasion capabilities of these cells were suppressed. Importantly, we detected an increased membranous expression and colocalization of β-CAT, E-CAD and EpCAM in the KLF4-overexpressing EpCAM−/CD133− non-stem cells, suggesting that this complex might be required for the cancer stem cell phenotype. Moreover, our in vivo xenograft studies demonstrated that with a KLF4 overexpression, EpCAM−/CD133− non-stem cells attained an in vivo tumor forming ability comparable to EpCAM+/CD133+ LCSCs, and the tumor specimens from KLF4-overexpressing xenografts had increased levels of both the KLF4 and EpCAM proteins. Additionally, we identified a correlation between the KLF4 and EpCAM protein expressions in human HCC tissues independent of the tumor stage and differentiation status. Collectively, our data suggest a novel function for KLF4 in modulating the de-differentiation of tumor cells and the induction of EpCAM+/CD133+ LCSCs in HuH7 HCC cells.

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Section: Isolation Of Lcscs and Non-stem Cells From Huh-7mentioning

confidence: 99%

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM−/CD133− nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7

Karagonlar

Akbari

Karabicici

et al. 2020

Cells

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“…Besides, Caja and Puerta also found the different abundance of IL-6 and TNF-α in the visceral and subcutaneous adipose tissues, with IL-6 ranging from 80 to 500 pg/100 mg tissues and TNF-α fewer than 10 pg/100 mg tissues ( 113 ). An in vitro experiment using cytokine array showed the high level of IL-6 in human adipocyte-conditioned media ( 114 ). An in vivo human experiment brought into a similar conclusion.…”

Section: Inflammatory Factors Of Bmas On Bone Metastasismentioning

confidence: 99%

“…With the increasing level of IL-6 produced by adipocytes, IL-6R was upregulated in EpCAMþ/CD133þ cancer stem cells. In this co-culture system, c-Met, STAT3 and ERK1/2 signaling pathways were activated, whereas Wingless-related integration site (Wnt)/β-catenin signaling was unchanged ( 114 ). BMA-derived IL-6 plays an indispensable role in tumor metastasis.…”

Section: Inflammatory Factors Of Bmas On Bone Metastasismentioning

confidence: 99%

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Bone Marrow Adipocyte: An Intimate Partner With Tumor Cells in Bone Metastasis

Luo

2018

Front. Endocrinol.

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The high incidences of bone metastasis in patients with breast cancer, prostate cancer and lung cancer still remains a puzzling issue. The “seeds and soil” hypothesis suggested that bone marrow (soil) may provide a favorable “niche” for tumor cells (seed). When seeking for effective ways to prevent and treat tumor bone metastasis, most researchers focus on tumor cells (seed) but not the bone marrow microenvironment (soil). In reality, only a fraction of circulating tumor cells (CTCs) could survive and colonize in bone. Thus, the bone marrow microenvironment could ultimately determine the fate of tumor cells that have migrated to bone. Bone marrow adipocytes (BMAs) are abundant in the bone marrow microenvironment. Mounting evidence suggests that BMAs may play a dominant role in bone metastasis. BMAs could directly provide energy for tumor cells, enhance the tumor cell proliferation, and resistance to chemotherapy and radiotherapy. BMAs are also known for releasing some inflammatory factors and adipocytokines to promote or inhibit bone metastasis. In this review, we made a comprehensive summary for the interaction between BMAs and bone metastasis. More importantly, we discussed the potentially promising methods for the prevention and treatment of bone metastasis. Genetic disruption and pharmaceutical inhibition may be effective in inhibiting the formation and pro-tumor functions of BMAs.

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“…4A). c-MET was found to be activated in cancer stem cells (36,37). We examined the expression of these proteins.…”

Section: Nell1 Induces Differentiation Of 95-d Lscssmentioning

confidence: 99%

Effect of NELL1 on lung cancer stem‑like cell differentiation

Zhai

Wei²,

Sha

et al. 2019

Oncol Rep

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The cancer stem cell theory recently has received enormous attention in cancer biology. Lung cancer stem-like cells are a subpopulation of undifferentiated lung tumor cells critical for lung cancer tumorigenesis, metastasis and resistance to therapy and disease relapse. The neural EGFL like 1 (NELL1) is a potent growth factor believed to preferentially target cells committed to the osteochondral lineage; yet, its expression and function in lung cancer are largely unknown. In the present study, we used specific medium to accumulate lung cancer stem-like cells of 95-D cells in spheres and obtained these highly expressed CD133 cells through flow cytometric cell sorting of CD133-stained cells which were termed 95-D lung cancer stem-like cells (95-D LCSCs). These 95-D LCSCs highly expressed stemness genes CD133, Oct4 and Sox2 determined by western blot analysis and quantitative real-time polymerase chain reaction (qPCR) analysis. Notably, we found that overexpression of NELL1 significantly reduced colony formation and invasion of 95-D LCSCs tested by soft agar colony formation and cell invasion assay. In addition, as determined by cell proliferation assay, overexpression of NELL1 increased the chemotherapeutic sensitivity of 95-D LCSCs to carboplatin and cisplatin. NELL1 also reduced the expression of phospho-MET (p-MET), Notch3 and HES1, which suggests that NELL1 may induce 95-D LCSC differentiation by inhibiting the expression of c-MET-Notch signaling. Our results suggest that NELL1 induces lung cancer stem-like cell differentiation, which provides a new potential therapeutic target for cancer stem cells.

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Effect of adipocyte-secreted factors on EpCAM+/CD133+ hepatic stem cell population

Cited by 12 publications

References 39 publications

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM−/CD133− nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM−/CD133− nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7

Bone Marrow Adipocyte: An Intimate Partner With Tumor Cells in Bone Metastasis

Effect of NELL1 on lung cancer stem‑like cell differentiation

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