2012
DOI: 10.1073/pnas.1018866109
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Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia

Abstract: Antiangiogenic therapy has been thought to hold significant potential for the treatment of cancer. However, the efficacy of such treatments, especially in breast cancer patients, has been called into question, as recent clinical trials reveal only limited effectiveness of antiangiogenic agents in prolonging patient survival. New research using preclinical models further suggests that antiangiogenic agents actually increase invasive and metastatic properties of breast cancer cells. We demonstrate that by genera… Show more

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Cited by 584 publications
(534 citation statements)
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References 40 publications
(43 reference statements)
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“…We made the distinction, however, that whereas CC proliferation increases with oxygen levels, CSC and ICC proliferation increases under hypoxic conditions. Therefore, we assume that in hypoxic conditions, the proliferation of CSCs and ICCs increases inversely with oxygen concentration, so that as oxygen concentration approaches 0, the proliferation rate is twice the rate at normal oxygen concentration (34).…”
Section: Methodsmentioning
confidence: 99%
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“…We made the distinction, however, that whereas CC proliferation increases with oxygen levels, CSC and ICC proliferation increases under hypoxic conditions. Therefore, we assume that in hypoxic conditions, the proliferation of CSCs and ICCs increases inversely with oxygen concentration, so that as oxygen concentration approaches 0, the proliferation rate is twice the rate at normal oxygen concentration (34).…”
Section: Methodsmentioning
confidence: 99%
“…S14). Finally, we assumed that the activity of immune cells is affected by tumor oxygenation (6,34,61). Owing to a lack of studies that directly relate oxygen levels to the data on the activity of NK or CD8 + T cells incorporated in our model, we used values from the range reported by de Pillis et al (53), whose model focuses on the action of NK and CD8 + T cells, with values of the model parameters specified by comparing model predictions with preclinical and clinical data.…”
Section: Methodsmentioning
confidence: 99%
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“…In breast cancer, about 200 CSCs is per 500 thousand of cancer cells, and in glioblastoma this proportion is 100 CSCs per 100 thousand tumor cells. Conley and co-workers [15] show that Bevacizumab, as well as Sunitinib induces the increase of CSCs amount in xenografts of breast cancer, via signalling pathway Akt/β-catenin, which is responsible for CSCs self-renewal. The increase of aldehyde dehydrogenase (ALDH) expression (marked by Aldefluor + ) proves the increase of CSCs.…”
Section: Tumor Resistance To Anti-angiogenic Therapymentioning
confidence: 99%