L’hypoxie tumorale

Hasmim, Meriem; Messai, Yosra; Noman, Muhammad Zaeem; Chouaı̈b, Salem

doi:10.1051/medsci/20143004017

Cited by 9 publications

(1 citation statement)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously published studies have demonstrated that the hypoxic microenvironment is a favorable condition for tumor cell growth and invasion ( 33 , 34 ). The key characteristic of HIF-1α is the promotion of angiogenesis, which is necessary for cancer tumor growth and invasion.…”

Section: Discussionmentioning

confidence: 99%

Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro

Chen

et al. 2015

International Journal of Molecular Medicine

View full text Add to dashboard Cite

A keloid scar is an overgrowth of dense fibrous tissue that develops around a wound. These scars are raised scars that spread beyong the margins of the orinigal wound to normal skin by invasion. Keloid tissue consists of both an epithelium and dermal fibroblasts. Recent studies have primarily focused on keloid fibroblasts; however, the precise role of keratinocytes in the invasion process of keloids remains to be identified. Hypoxia is a typical characteristic of keloid scars, as well as other solid tumors. The expression of the transcription factor, hypoxia-inducible factor-1α (HIF-1α), is mainly induced by hypoxia and is known for its ability to induce proliferative and transformative changes in cells; its expression has been shown to correlate with tumor invasion and metastasis. In the present study, we used immunohistochemistry, fluorescence staining and western blot analysis and demonstrated that HIF-1α was highly expressed in both the epithelial layer of keloid tissue specimens and in hypoxia-exposed keratinocytes, which suggested that the keloid keratinocytes underwent epithelial-to-mesenchymal transition (EMT) in vitro. The high expression of mesenchymal markers, such as as vimentin and fibronectin was confirmed, as well as the reduced expression of E-cadherin and zonula occludens-1 (ZO-1) during this process by detection at the protein and mRNA level. Moreover, siRNA targeting HIF-1α reversed the changes which had occurred in the morphology of the keratinocytes (cells had acquired a fibroblast-like appearance) and suppressed the invasive ability of the keratinocytes. In conclusion, the present findings demonstrate that the hypoxia/HIF-1α microenvironment provides a favorable environment for keloid-derived keratinocytes to adopt a fibroblast-like appearance through EMT. This transition may be responsible for the enhanced capacity of keloid keratinocytes to invade, allowing the keloids to extend beyond the wound margin.

show abstract

Section: Discussionmentioning

confidence: 99%

Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro

Chen

et al. 2015

International Journal of Molecular Medicine

View full text Add to dashboard Cite

show abstract

Interpretation of immunohistochemistry data of tumor should consider microenvironmental factors

Bian

Zhang

et al. 2015

Tumor Biol.

View full text Add to dashboard Cite

The influence of tumor surrounding microenvironment is often neglected when immunohistochemistry is performed to investigate tumor properties and search biomarkers of cancer. This study was designed to evaluate whether the influence of tumor microenvironment on biological features of tumor cells should be taken into account for interpretation of the immunohistochemistry data of tumor specimens. In this study, we showed an example by using three tumor cell lines (HeLa, WSU-HN6, and Tca83) to establish tumor-caused bone destruction models in nude mice and then to investigate the influence of bone marrow microenvironment (BMM) on biological features of tumor cells. Immunohistochemistry results showed that, compared with tumor cells located outside of BMM, tumor cells located inside of BMM presented huge differences in the expression of inflammation-related proteins including tumor necrosis factor-α (TNF-α), TNF receptor-associated factor protein-6 (TRAF-6), phosphorylated-NF-κB p65 (p-p65), interleukin (IL)-6 and IL-11, matrix metalloproteinases including MMP-1, MMP-2, MMP-9, and MMP-13; and osteogenesis-related proteins including runt-related transcription factor 2 (RUNX2), bone sialoprotein (BSP), and osteocalcin (OCN) in all the models. However, when we compared the cell line pair derived from different sites (outside and inside of BMM, respectively) of the same HeLa tumor sample by real-time PCR, Western blot, and immunocytochemistry, the differences aforementioned in tumor tissues were not found. In addition, we verified that normal human bone marrow could not cause the above changes detected in vivo. Our results suggested that tumor-modified microenvironment could give the new biological features of the invaded tumor cells. Therefore, we should consider the influence of the surrounding microenvironment on tumor cells when we analyze tumor properties using immunohistochemistry.

show abstract

Correlation of immunohistochemical expression of HIF-1alpha and IDH1 with clinicopathological and therapeutic data of moroccan glioblastoma and survival analysis

Sfifou

Hakkou²,

Bouaïti

et al. 2021

Annals of Medicine &Amp; Surgery

View full text Add to dashboard Cite

Introduction Glioblastomas are aggressive primary intracranial tumours of the central nervous system causing significant mortality and morbidity worldwide. Objective This study aims to evaluate the prognostic value of tissue expression by immunostaining of hypoxia-inducible factor (HIF-1α), isocitrate dehydrogenase 1 (IDH1), and tumour protein p53 in glioblastoma in Moroccan patients. The association of HIF-1α, IDH1, and p53 expression with the clinicopathological data and overall patient survival (OS) was also evaluated. Materials and methods Confirmed glioblastomas were included in this study. Twenty-two tissue samples were obtained by neurosurgical intervention resulting from total resection, and subtotal resection or biopsy. Karnofsky index, histological type of tumour, and the status of IDH1, p53 protein, and HIF-1α expression by immunostaining were reported. Results The majority of the patients were males (64%) with a sex ratio of 1.75. The average age was 54 ± 13. Median follow-up was 10.10 months and median overall survival was 10 months. The expression of HIF-1α was high in 10 samples (45%) and low in 12 (55%). There was a statistically significant difference in OS of 85% at 12 months for the subgroup of patients “HIF-1α negative IDH1 positive” p = 0.038, the unadjusted analysis showed that the group “HIF-1α positive, IDH1 positive” was a poor prognostic factor, the HR was 0.08 (95% CI: 0.009–0.756, p = 0.027). Conclusion Patients with negative HIF-1α expression and positive IDH1 expression have a better prognosis, suggesting that these two biomarkers may be useful in the search for new approaches for targeted therapy in glioblastoma.

show abstract

L’hypoxie tumorale

Cited by 9 publications

References 51 publications

Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro

Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro

Interpretation of immunohistochemistry data of tumor should consider microenvironmental factors

Correlation of immunohistochemical expression of HIF-1alpha and IDH1 with clinicopathological and therapeutic data of moroccan glioblastoma and survival analysis

Contact Info

Product

Resources

About