Anthracycline Inhibits Recruitment of Hypoxia-inducible Transcription Factors and Suppresses Tumor Cell Migration and Cardiac Angiogenic Response in the Host

Tanaka, Tetsuhiro; Yamaguchi, Junna; Shoji, Keisuke; Nangaku, Masaomi

doi:10.1074/jbc.m112.374587

Cited by 43 publications

(43 citation statements)

References 32 publications

(13 reference statements)

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“…Notably, in these clinical trials, the combination of agents with antiangiogenic properties and other chemotherapeutic agents may not lend itself to an accurate interpretation of the influence of distinct, preexisting angiogenic programs on the chemotherapy response. Nevertheless, among breast cancer subtypes, TNBC may perhaps respond best to antiangiogenic therapy (46,47 (49,50). Angpt2 is among the targets of HIF-1 (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Kim¹,

Sampaio²,

Lundy³

et al. 2016

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Kim¹,

Sampaio²,

Lundy³

et al. 2016

JCI Insight

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“…17,22 Immunoblotting Immunoblotting was performed as described previously. 23 The primary antibodies used for immunoblotting were anti-SPAG4 …”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

Sperm-Associated Antigen 4, a Novel Hypoxia-Inducible Factor 1 Target, Regulates Cytokinesis, and Its Expression Correlates with the Prognosis of Renal Cell Carcinoma

Shoji

Murayama

Mimura

et al. 2013

The American Journal of Pathology

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Hypoxia plays a crucial role in many pathophysiological conditions, including cancer biology, and hypoxia-inducible factor (HIF) regulates transcriptional responses under hypoxia. To elucidate the cellular responses to hypoxia, we performed chromatin immunoprecipitation with deep sequencing in combination with microarray analysis and identified HIF-1 targets. We focused on one of the novel targets, sperm-associated antigen 4 (SPAG4), whose function was unknown. SPAG4, an HIF-1-specific target, is up-regulated in various cultured cells under hypoxia. Examination of SPAG4 expression using a tissue microarray consisting of 190 human renal cell carcinoma (RCC) samples revealed that SPAG4 is an independent prognostic factor of cancer-specific mortality. Live-cell imaging revealed localization of SPAG4 at the intercellular bridge in telophase. We also studied cells in which SPAG4 was knocked down. Hypoxia enhances tetraploidy, which disturbs cell proliferation, and knockdown of SPAG4 increased tetraploid formation and decreased cell proliferation under both normoxic and hypoxic conditions. Studies using deletion mutants of SPAG4 also suggested the involvement of SPAG4 in cytokinesis. Microarray analysis confirmed dysregulation of cytokinesis-related genes by knockdown of SPAG4. In conclusion, SPAG4 is an independent prognostic factor in RCC and plays a crucial role in cytokinesis to defend against hypoxia-induced tetraploid formation. This defensive mechanism may promote survival of cancer cells under hypoxic conditions, thus leading to poor prognosis.

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“…Previous work demonstrates that taxanes and anthracyclines can downregulate vascular endothelial growth factor and other signaling molecules and may explain a reduction in angiogenesis. 38–41 Taken together, our data indicates that radiation and chemotherapy can impair vascular penetrance of an implanted ADM scaffold in breast reconstruction.…”

Section: Discussionmentioning

confidence: 57%

Remodeling Characteristics and Collagen Distributions of Biologic Scaffold Materials Biopsied From Postmastectomy Breast Reconstruction Sites

Cavallo

Gangopadhyay

Dudas

et al. 2015

Annals of Plastic Surgery

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OBJECTIVE The study purpose was to evaluate the associations between patient characteristics and the histologic remodeling scores of acellular dermal matrices (ADMs) biopsied from breast reconstruction sites in the first attempt to generate a multivariable risk prediction model of non-constructive remodeling. It was hypothesized that host characteristics and surgical site assessments predict the degree of graft remodeling for ADMs used during breast reconstruction. METHODS ADMs were biopsied from the breast reconstruction sites of n=62 patients during a subsequent breast procedure, stained with Hematoxylin and Eosin, and evaluated according to a semi-quantitative scoring system for remodeling characteristics [cell types (CT), cell infiltration (CI), extracellular matrix (ECM) deposition, scaffold degradation (SD), fibrous encapsulation (FE), and neovascularization (NEO)] and a mean composite score (CR). Biopsies were stained with Sirius Red and Fast Green, and analyzed to determine the collagen I:III ratio. Based on univariate analyses between subject clinical characteristics and the histologic remodeling scores, cohort variables were selected for multivariable regression models using a p ≤0.20. RESULTS The CR score model yielded 3 variables: pack-year history, corticosteroid use, and radiation timing (r2pseudo=0.81). The model for collagen I yielded 2 variables: corticosteroid use and reason for reoperation (r2pseudo=0.78). The model for collagen III yielded 1 variable: reason for reoperation (r2pseudo=0.35). CONCLUSION These preliminary results constitute the first steps in generating a risk prediction model that predicts the patients and clinical circumstances most likely to experience non-constructive remodeling of biologic grafts used to reconstruct the breast.

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Anthracycline Inhibits Recruitment of Hypoxia-inducible Transcription Factors and Suppresses Tumor Cell Migration and Cardiac Angiogenic Response in the Host

Cited by 43 publications

References 32 publications

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Sperm-Associated Antigen 4, a Novel Hypoxia-Inducible Factor 1 Target, Regulates Cytokinesis, and Its Expression Correlates with the Prognosis of Renal Cell Carcinoma

Remodeling Characteristics and Collagen Distributions of Biologic Scaffold Materials Biopsied From Postmastectomy Breast Reconstruction Sites

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