Evidence for Nutrient Modulation of Tumor Phenotype: Impact of Tyrosine and Phenylalanine Restriction

AbstractRegulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may directly modify tumor behavior. Here we show that inhibition of miRNAs -503 and -23a, alone or in combination, enhances tumor proliferation in hepatocyte and non-hepatocyte derived cancers in vitro, driving more aggressive tumor behavior in vivo. Inhibition of miRNA-152 caused induction of DNMT1, site-specific methylation with associated changes in gene expression and in vitro and in vivo growth inhibition. Enforced changes in expression of two miRNA recapitulating changes observed in failed regeneration led to complete growth inhibition of multi-lineage cancers in vivo. Our results indicate that regulation of regeneration and tumor aggressiveness are concordant and that miRNA-based inhibitors of regeneration may constitute a novel treatment strategy for human cancers.

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Towards a ‘hot’ tumor phenotype: DKN-01 sensitizes the tumor micro-environment via pro-immune cell cytokine release in vitro and ex vivo

Gynecologic Oncology ◽

10.1016/s0090-8258(21)00670-3 ◽

2021 ◽

Vol 162 ◽

pp. S12

Author(s):

Jhalak Dholakia ◽

Jaclyn Wall ◽

Carly Bess Scalise ◽

Ashwini Katre ◽

Rebecca Arend

Keyword(s):

Immune Cell ◽

Ex Vivo ◽

Cytokine Release ◽

Tumor Phenotype ◽

Release In Vitro

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Antigenic and Genotypic Similarity between Primary Glioblastomas and Their Derived Neurospheres

Journal of Oncology ◽

10.1155/2011/314962 ◽

2011 ◽

Vol 2011 ◽

pp. 1-16 ◽

Cited By ~ 14

Author(s):

Valentina Caldera ◽

Marta Mellai ◽

Laura Annovazzi ◽

Angela Piazzi ◽

Michele Lanotte ◽

...

Keyword(s):

Stem Cells ◽

Genetic Alterations ◽

Tumor Stem Cells ◽

Primary Tumors ◽

Immunodeficient Mice ◽

Brain Tumor Stem Cells ◽

Tumor Phenotype ◽

Fetal Bovine ◽

Primary Glioblastomas

Formation of neurospheres (NS) in cultures of glioblastomas (GBMs), with self-renewal, clonogenic capacities, and tumorigenicity following transplantation into immunodeficient mice, may denounce the existence of brain tumor stem cells (BTSCs) in vivo. In sixteen cell lines from resected primary glioblastomas, NS showed the same genetic alterations as primary tumors and the expression of stemness antigens. Adherent cells (AC), after adding 10% of fetal bovine serum (FBS) to the culture, were genetically different from NS and prevailingly expressed differentiation antigens. NS developed from a highly malignant tumor phenotype with proliferation, circumscribed necrosis, and high vessel density. Beside originating from transformed neural stem cells (NSCs), BTSCs may be contained within or correspond to dedifferentiated cells after mutation accumulation, which reacquire the expression of stemness antigens.

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Cells Silenced for SDHB Expression Display Characteristic Features of the Tumor Phenotype

Cancer Research ◽

10.1158/0008-5472.can-07-5580 ◽

2008 ◽

Vol 68 (11) ◽

pp. 4058-4067 ◽

Cited By ~ 59

Author(s):

Ana M. Cervera ◽

Nadezda Apostolova ◽

Francisco Luna Crespo ◽

Manuel Mata ◽

Kenneth J. McCreath

Keyword(s):

Tumor Phenotype ◽

Characteristic Features

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Fetal Alcohol Exposure Increases Mammary Tumor Susceptibility and Alters Tumor Phenotype in Rats

Alcoholism Clinical and Experimental Research ◽

10.1111/j.1530-0277.2010.01276.x ◽

2010 ◽

Vol 34 (11) ◽

pp. 1879-1887 ◽

Cited By ~ 31

Author(s):

Tiffany A. Polanco ◽

Catina Crismale-Gann ◽

Kenneth R. Reuhl ◽

Dipak K. Sarkar ◽

Wendie S. Cohick

Keyword(s):

Mammary Tumor ◽

Alcohol Exposure ◽

Fetal Alcohol Exposure ◽

Fetal Alcohol ◽

Tumor Susceptibility ◽

Tumor Phenotype

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Circulating estradiol defines the tumor phenotype in menopausal breast cancer patients

Maturitas ◽

10.1016/j.maturitas.2009.07.001 ◽

2009 ◽

Vol 64 (1) ◽

pp. 43-45 ◽

Cited By ~ 7

Author(s):

José Schneider ◽

Silvia Martín-Gutiérrez ◽

Jesús A. Tresguerres ◽

Juan A. García-Velasco

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Tumor Phenotype

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Concordance Between ER, PR, HER2 neu Receptors Before and After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Forum of Clinical Oncology ◽

10.2478/fco-2019-0021 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Heba F. Taha ◽

Ola M. Elfarargy ◽

Reham A. Salem ◽

Doaa Mandour ◽

Amira A. Salem ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Her2 Status ◽

Breast Cancer Patients ◽

Before And After ◽

Tumor Phenotype

Abstract Background Introducing neoadjuvant chemotherapy (NCT) in a breast cancer patient may be associated with changes in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) status. Method In our prospective cohort study, we evaluated the impact of change in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) on the prognosis of breast cancer patients treated with neoadjuvant chemotherapy (NCT). We investigated 110 patients with locally advanced breast cancer for ER, PR and HER2 status of their lesions before and after NCT. Result For hormone receptor status (HR) (which include ER, PR) of the residual tumor of the patients after receiving NCT, 12 (10.9%) of them changed from HR (+) to HR (−) and 15 (13.6%) changed from HR (−) to HR (+). For HER2 status after NCT, 8 (7.3%) patients changed from HER2 (+) to HER2 (−) and 9 (8.2%) patients changed from HER2 (−) to HER2 (+). Triple negative (TN) tumor phenotype changes occurred in 17 (15.5%) patients. Patients for whom the HR status changed from positive to negative had poor prognosis for both disease-free survival (DFS) and overall survival (OS) in univariate survival analysis. Conclusion Changes in ER, PR, HER2 status and tumor phenotype in breast cancer patients after NCT had a negative prognostic impact and were associated with a poor prognosis.

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Detachment Stress Mediated Bioenergetic Switch of Malignant Melanoma Cells Into Anti-Warburg Phenotype

10.21203/rs.3.rs-855821/v1 ◽

2021 ◽

Author(s):

WuChing Uen ◽

TingTing Tseng ◽

Ching-Po Wu ◽

ShaoChen Lee

Keyword(s):

Drug Sensitivity ◽

Aerobic Glycolysis ◽

Metastatic Tumor ◽

Melanoma Cells ◽

Glucose Depletion ◽

Electron Transport Chains ◽

Tumor Phenotype ◽

Metastatic Process ◽

Potential Therapeutics ◽

A375 Cells

Abstract One of the biological features of cancer cells was their aerobic glycolysis by extensive glucose fermentation to harvest energy, so called Warburg effect. Melanoma is one of the most aggressive human cancers with poor prognosis and high mortality for its high metastatic ability. During the metastatic process, the metastatic tumor cells should survive under detachment stress. However, whether the detachment stress could affect the tumor phenotype was worthy to investigate. We had established human melanoma A375 cells under detachment stress, which mimicked circulating melanoma. It was shown the detachment stress altered melanoma cell activities, malignancy, and drug sensitivity. In this study, we found that adherent melanoma cells were more sensitive to glucose depletion. However, detachment stress reduced lactate secretion owing to the reduced MCT4 and GLUT1 expressions, the altered glycolytic and respiratory capacities, and the increased superoxide production. Detachment stress also increase the sensitivity of melanoma cells toward blockade of electron transport chains. Investigation of the change in glucose metabolism of melanoma cells under detachment stress would be critical to provide novel molecular mechanism to develop potential therapeutics

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