Surgical management of brain metastases

Ranasinghe, Moksha; Sheehan, Jonas M.

doi:10.3171/foc.2007.22.3.3

Cited by 51 publications

(43 citation statements)

References 41 publications

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“…However, although therapies for primary tumors and extracranial metastases are improving, effective treatments for brain metastases are still missing (1)(2)(3). Our data define the activated, high-affinity conformer of tumor cell integrin ␣ v ␤ 3 as a potential new therapeutic target in brain metastasis.…”

Section: Discussionmentioning

confidence: 95%

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Activation of tumor cell integrin α _v β ₃ controls angiogenesis and metastatic growth in the brain

Lorger

Krueger

O'Neal

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

162

123

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The incidence of brain metastasis is rising and poses a severe clinical problem, as we lack effective therapies and knowledge of mechanisms that control metastatic growth in the brain. Here we demonstrate a crucial role for high-affinity tumor cell integrin ␣v␤3 in brain metastatic growth and recruitment of blood vessels. Although ␣v␤3 is frequently up-regulated in primary brain tumors and metastatic lesions of brain homing cancers, we show that it is the ␣v␤3 activation state that is critical for brain lesion growth. Activated, but not non-activated, tumor cell ␣v␤3 supports efficient brain metastatic growth through continuous up-regulation of vascular endothelial growth factor (VEGF) protein under normoxic conditions. In metastatic brain lesions carrying activated ␣v␤3, VEGF expression is controlled at the post-transcriptional level and involves phosphorylation and inhibition of translational respressor 4E-binding protein (4E-BP1). In contrast, tumor cells with nonactivated ␣v␤3 depend on hypoxia for VEGF induction, resulting in reduced angiogenesis, tumor cell apoptosis, and inefficient intracranial growth. Importantly, the microenvironment critically influences the effects that activated tumor cell ␣v␤3 exerts on tumor cell growth. Although it strongly promoted intracranial growth, the activation state of the receptor did not influence tumor growth in the mammary fat pad as a primary site. Thus, we identified a mechanism by which metastatic cells thrive in the brain microenvironment and use the high-affinity form of an adhesion receptor to grow and secure host support for proliferation. Targeting this molecular mechanism could prove valuable for the inhibition of brain metastasis.angiogenesis ͉ brain metastasis ͉ integrin activation ͉ 4E-BP1 B rain metastases are diagnosed in 10% to 40% of patients with progressing cancer, and the incidence is rising as patients live longer and extracranial metastases respond to improved treatments. However, brain metastases still cannot be treated effectively, and mechanisms controlling brain metastatic growth are largely unknown (1-3).Here, we demonstrate that the high-affinity state of tumor cell adhesion receptor integrin ␣ v ␤ 3 critically promotes metastatic growth and recruitment of supporting blood vessels within the brain microenvironment. Integrins are cell surface receptors composed of non-covalently linked ␣ and ␤ subunits that mediate cell-matrix and cell-cell interactions and transduce signals that have impacts on cell survival, proliferation, adhesion, migration, and invasion. Integrin signals can also originate inside cells, affect receptor affinity, and thereby control ligand binding, cross talk with other receptors, and alter cell adhesion and proliferation (4-6). Integrin ␣ v ␤ 3 also plays a role on sprouting endothelial cells and contributes to angiogenesis (7). In several tumor types, including glioma, breast cancer, and melanoma, expression of ␣ v ␤ 3 supports invasion and metastasis (8-11). Notably, these tumors either originate in the brain or freque...

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Section: Discussionmentioning

confidence: 95%

“…However, brain metastases still cannot be treated effectively, and mechanisms controlling brain metastatic growth are largely unknown (1)(2)(3).…”

mentioning

confidence: 99%

Activation of tumor cell integrin α _v β ₃ controls angiogenesis and metastatic growth in the brain

Lorger

Krueger

O'Neal

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

162

123

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“…Thus, at first glance, it would seem that metastatic brain tumor surgery has been established. However, in fact, the local recurrence rate is high in the case of surgical resection alone, and attempts are being made to improve the local recurrence rate by performing follow-up treatments such as whole-brain irradiation, stereotactic radiosurgery on the resection cavity, or local chemotherapy (Sills 2005; Kim et al 2006;Mathieu et al 2006;Ewend et al 2007;Ranasinghe and Sheehan 2007). The high local recurrence rate following surgical resection alone clearly implies the presence of residual tumor tissue (Patchell et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Surgical Technique for Metastatic Brain Tumors

Okuda¹,

Kato²

2011

Diagnostic Techniques and Surgical Management of Brain Tumors

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“…Predictors that favor a surgical benefit include: single or few metastases, tumor location, surgical accessibility, KPS > 70, patient age < 65 years, local mass effect, control of extracranial disease, and absence of leptomeningeal involvement. [57] Based on the therapy oncology group database, patients of RPA class I are likely to benefit from surgery, whereas patients of RPA class III are not. [40] The primary goal of surgery is either macroscopic gross total resection or decompression dependent on the aforementioned predictors.…”

Section: Local Therapeutic Strategies: Neurosurgical Intervention Andmentioning

confidence: 99%

Interdisciplinary management of central nervous system metastasis and neoplastic meningitis: recent developments and future perspectives

Tabatabai¹,

Koch²,

Roggia³

et al. 2016

JCMT

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The incidence of metastatic disease in the central nervous system (CNS) is rising. According to current estimates, up to a third of adult cancer patients will suffer from CNS metastasis. Clinical evidence-based data from prospective randomized trials are rare, however, because CNS metastasis patients were often excluded from clinical trial participation. The management of CNS metastasis patients is therefore rather ill-defined and an interdisciplinary challenge. Recent basic and translational science data have begun contributing to a more profound understanding of the molecular mechanisms leading to invasion of tumor cells into the CNS. This report reviews advances, challenges, and perspectives in this field.

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Surgical management of brain metastases

Cited by 51 publications

References 41 publications

Activation of tumor cell integrin α _v β ₃ controls angiogenesis and metastatic growth in the brain

Activation of tumor cell integrin α _v β ₃ controls angiogenesis and metastatic growth in the brain

Surgical Technique for Metastatic Brain Tumors

Interdisciplinary management of central nervous system metastasis and neoplastic meningitis: recent developments and future perspectives

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Surgical management of brain metastases

Cited by 51 publications

References 41 publications

Activation of tumor cell integrin α v β 3 controls angiogenesis and metastatic growth in the brain

Activation of tumor cell integrin α v β 3 controls angiogenesis and metastatic growth in the brain

Surgical Technique for Metastatic Brain Tumors

Interdisciplinary management of central nervous system metastasis and neoplastic meningitis: recent developments and future perspectives

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Activation of tumor cell integrin α _v β ₃ controls angiogenesis and metastatic growth in the brain

Activation of tumor cell integrin α _v β ₃ controls angiogenesis and metastatic growth in the brain