The Contribution of Angiogenesis to the Process of Metastasis

Bielenberg, Diane R.; Zetter, Bruce R.

doi:10.1097/ppo.0000000000000138

Cited by 430 publications

(322 citation statements)

References 74 publications

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“…Tumor angiogenesis, the process by which tumors form new blood vessels from established ones, plays a critical role in tumor growth and metastasis (Kerbel, 2008; Bielenberg & Zetter, 2015). Many tumors produce proangiogenic factors such as VEGF-A (abbreviated VEGF), which promotes tumor progression by (1) paracrine actions on endothelial cells, resulting in increased proliferation and migration as well as enhanced vascular permeability; and (2) autocrine actions on tumor cells, which express VEGF receptors.…”

Section: Metastasis Enablermentioning

confidence: 99%

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

Malin

Petrovič

Strekalova

et al. 2016

Pharmacology & Therapeutics

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αB-crystallin is a widely expressed member of the small heat shock protein family that protects cells from stress by its dual function as a molecular chaperone to preserve proteostasis and as a cell death antagonist that negatively regulates components of the conserved apoptotic cell death machinery. Deregulated expression of αB-crystallin occurs in a broad array of solid tumors and has been linked to tumor progression and poor clinical outcomes. This review will focus on new insights into the molecular mechanisms by which oncogenes, oxidative stress, matrix detachment and other tumor microenvironmental stressors deregulate αB-crystallin expression. We will also review accumulating evidence pointing to an essential role for αB-crystallin in the multi-step metastatic cascade whereby tumor cells colonize distant organs by circumventing a multitude of barriers to cell migration and survival. Finally, we will evaluate emerging strategies to therapeutically target αB-crystallin and/or interacting proteins to selectively activate apoptosis and/or derail the metastatic cascade in an effort to improve outcomes for patients with metastatic disease.

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Section: Metastasis Enablermentioning

confidence: 99%

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

Malin

Petrovič

Strekalova

et al. 2016

Pharmacology & Therapeutics

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“…One of the most important issues in tumors treatment is the limited ability of chemotherapeutic drugs to effectively penetrate tissues and reach all cancer cells at high enough concentrations to inhibit tumor growth. The ability of a molecule to penetrate neoplastic tissue depends on its own physicochemical properties but also on the tumor vascularization and interstitial pressure which depend not only on cancer cell growth but also on the tumor microenvironment34. This microenvironment has a poorly organized vasculature that permits the formation of hypoxic areas with increased interstitial fluid pressure, so they are hard to reach for chemotherapeutic drugs56.…”

mentioning

confidence: 99%

3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

Giordano

Morosi

Veglianese

et al. 2016

Sci Rep

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Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse.

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“…Tumor angiogenesis is a key process for the majority of solid tumors, since the growth and metastasis of malignant cells require the formation of new blood vessels (5)(6)(7)15,16). Tumstatin specifically inhibits endothelial cell proliferation and induces apoptosis by interacting with α V β 3 integrin (12,17).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it is the process by which tumor cells are provided with a supply of blood and nutrients (5)(6)(7). Due to its extensive role in inducing cancer cell growth, tumor angiogenesis has become a novel and promising target for anticancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Vector-mediated Tum-5 expression in neovascular endothelial cells for treating hepatocellular carcinoma

Guan

Sun

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Hypervascular hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortality. Angiogenesis is an important contributor to HCC progression and metastasis; therefore, inhibiting angiogenesis may be an effective method of treating HCC. Tumstatin is a novel type of efficient endogenous vascular endothelial cell growth inhibiting factor. The anti-angiogenic activity of tumstatin is localized to the 54-132 amino acid region (Tum-5). In a previous study performed by our group, the gene fragment encoding Tum-5 was cloned and inserted into a pLXSN retroviral vector. In the present study, the anti-angiogenic effects of Tum-5 and the antitumor effects exerted by the pLXSN-Tum-5 vector in vivo were investigated. The results demonstrated that pLXSN-Tum-5 significantly inhibited the growth of human umbilical vein endothelial cells compared with pLXSN, but had no obvious effect on HepG2 cell growth. Moreover, the antitumor and anti-angiogenic activity of Tum-5 was examined in vivo using a xenograft of H22 HCC cells. The results indicated that pLXSN-Tum-5 significantly inhibited tumor growth following 5 injections over 10 days. The size and weight of tumors in the pLXSN-Tum-5 group were lower than those in the saline and pLXSN groups. Furthermore, immunohistochemical analysis with CD31 antibodies indicated that the average microvessel density in the pLXSN-Tum-5 group were significantly lower than that in the saline and pLXSN groups. These results suggested that Tum-5 exerts its antitumor activity by suppressing vascular endothelial cells. The gene fragment of Tum-5 may be developed as an effective inhibitor of angiogenesis and used to treat patients with HCC.

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The Contribution of Angiogenesis to the Process of Metastasis

Cited by 430 publications

References 74 publications

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

Vector-mediated Tum-5 expression in neovascular endothelial cells for treating hepatocellular carcinoma

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