Relationship between angiogenesis and metastasis

Role of angiogenesis in cancer invasion and metastasis

relationship between angiogenesis and metastasis

Annu Rev Med. ; Angiogenesis and tumor metastasis. Zetter BR( 1). Author information: (1)Children's Hospital, Harvard Medical School, Boston. A strong correlation has been found between VEGF expression and In addition to sprouting angiogenesis, especially metastases may initially. The 4 major steps of endothelial cells in angiogenesis. 1. . Tumor growth and metastatic progression .. Correlation between EMT inducing TFs with the.

relationship between angiogenesis and metastasis

Advanced Search Abstract Background and Purpose: The microscopic detection of tumor cells micrometastases in bone marrow and the extent of blood vessel formation angiogenesis in primary tumor specimens are recognized as independent prognostic markers in patients with breast cancer.

Since micrometastases occur as a consequence of interaction between the neoplastic cells and the tumor neovasculature, we have examined the relationship between these markers to determine whether the degree of angiogenesis is related to the presence of micrometastases.

Is the relationship between angiogenesis and metastasis in breast cancer real?

Micrometastases were identified in bone marrow aspirates collected from multiple sites in breast cancer patients prior to surgery mastectomy or lumpectomy. Tumor cells were detected through an examination of epithelial membrane antigen expression and an analysis of cell morphology. Tumor vascularity was graded semiquantitatively or quantitatively Chalkley point count after immunohistochemical staining of the CD31 antigen expressed by the endothelial cells.

The reproducibility and accuracy of the vascular grading were validated by use of kappa statistics.

Is the relationship between angiogenesis and metastasis in breast cancer real?

Associations between micrometastases and clinicopathologic characteristics, including angiogenesis, were examined using chi-squared and logistic regression techniques. All tests of statistical significance were twosided. This study suggests that an assessment of tumor angiogenesis and vascular invasion gives a reliable indication of the likelihood of the presence of bone marrow micrometastases in patients with breast cancer and that both processes contribute to metastases.

Despite apparent curative surgery, a large proportion of lymph node-negative breast cancer patients will die of metastatic disease that is undetected by conventional methods at presentation. In some studies, bone marrow micrometastases identified by immunohistochemistry at primary surgery have predicted disease progression and have been associated with a significant reduction in relapse-free and overall survival in several tumor types, including breast carcinomas 1 -— 8.

Therefore, it has been suggested that examination for bone marrow micrometastasis in breast cancer patients would be useful as a prognostic marker and would help to define and monitor patient groups who are at high risk and who would benefit from adjuvant therapy.

relationship between angiogenesis and metastasis

Angiogenesis, the development of new vessels from the existing vasculature, is essential for tumor growth 9. The angiogenic activity of a tumor as assessed by microvessel density has been shown to be a powerful independent prognostic factor in many tumor types, including breast carcinoma 10 — Because interaction between this neovasculature and neoplastic cells results in metastasis, we have examined the relationship between angiogenesis and bone marrow micrometastases in a series of breast cancer patients to determine whether the extent of angiogenesis is related to the presence of bone marrow micrometastases.


Subjects and Methods Patients. From a cohort of female patients with primary breast cancer in which the relationship between bone marrow micrometastases and other clinicopathologic features had been previously reported 13with data and material were available for use for this study. This series of patients is, however, different from those studied by our group for quantitative assessment of angiogenesis. The patient group had a median age of 61 years range, yearshad been previously treated by mastectomy or lumpectomy 63 and patients, respectively depending on the size and site of the tumor, and had been administered adjuvant hormonal and chemotherapy treatment 36 and 52 patients, respectively.

relationship between angiogenesis and metastasis

Written informed consent was obtained from the patients, and the protocol was approved by the Hospital Ethical Committee. Estrogen receptor expression was measured by the dextran-coated charcoal method Additionally, the availability of a transgenic zebrafish line that expresses enhanced green fluorescent protein allows us to study the interaction between tumor cells and the vasculature in a non-invasive manner.

We also developed a novel hypoxia chamber in which oxygen levels in the aquarium can be adjusted to a certain desired level. Development of these novel methods allows us to study the early events of cancer metastasis, which otherwise cannot be visualized in mammalian systems.

Angiogenesis and tumor metastasis.

In paper II, we studied the role of hypoxia in promoting metastasis using the method described in Paper I. We have found that hypoxia induces angiogenesis in the implanted tumors and VEGF is the crucial mediator that is responsible for hypoxia-induced tumor angiogenesis.

relationship between angiogenesis and metastasis

To further validate the role of VEGF in mediating tumor invasion and metastasis, blocking VEGFR signaling by tyrosine kinase inhibitors or specific morpholinos inhibits hypoxia-induced metastasis.

Moreover, overexpression of VEGF in tumor cells also significantly promotes cancer metastasis through stimulation of tumor angiogenesis although VEGF lacks direct effects on tumor cells.

These findings show that hypoxia plays a pivotal role in facilitating tumor cell dissemination at the early stage of the metastatic cascade and inhibition of the VEGF signaling might be an important approach for treatment of metastatic disease.

How does cancer spread through the body? - Ivan Seah Yu Jun

Via this mechanism, filamin A stimulates tumor angiogenesis and tumor growth. In paper IV, we show that filamin B serves as a negative regulator for tumor invasion and metastasis. In filamin B deficient mice, increased metalloproteinase-9 MMP-9 activity has been detected.

Similarly, silencing of MMP-9 in various tumor models resulted in enhanced tumor angiogenesis and invasion by increasing the bioavailability of VEGF.

relationship between angiogenesis and metastasis