Angiogenesis: molecular mechanisms and functional interactions

2003 ◽  
Vol 89 (01) ◽  
pp. 190-197 ◽  
Author(s):  
Georg Breier ◽  
Hellmut Augustin
Keyword(s):  
Growth Factors ◽  
Research Program ◽  
Tumor Invasion ◽  
Molecular Mechanisms ◽  
Precursor Cells ◽  
Invasion And Metastasis ◽  
Angiogenic Growth Factors ◽  
Cell Contacts ◽  
Functional Interactions ◽  
Biannual Meeting

SummaryThe German Priority Research Program “Angiogenesis” (www.angiogenese.de) hosts a biannual meeting in the Kloster Seeon in Southern Germany. The 2nd Kloster Seeon Meeting “Angiogenesis: Molecular Mechanisms and Functional Interactions” was held in September 2002. It included sessions on hypoxia, the biology of endothelial precursor cells, angiogenic growth factors including VEGFs, the angiopoietins, ephrins, and FGFs, mechanisms of vascular sprouting and cell-cell contacts during angiogenesis, angiogenic signaling, lymphangiogenesis, angiogenesis during tumor invasion and metastasis, and on novel angiomanipulatory therapies. This report summarizes the key findings reported during the platform presentations of the meeting.

Mutant Ras-Expressing Fibroblasts Induce Expansion of Circulating Angio- and Lymphangiogenic Precursor Cells: Potential Role in Tumour Vascularisation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1331-1331
Author(s):  
Robert J. Knight ◽  
Tracey A. O’Brien ◽  
Robert Lindeman ◽  
Alla Dolnikov
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Vascular System ◽  
Ex Vivo ◽  
Tumour Microenvironment ◽  
Precursor Cells ◽  
Ras Signaling ◽  
Cancer Therapies ◽  
Angiogenic Growth Factors ◽  
Extracellular Matrix Components

Abstract Fibroblasts have a prominent role in the initiation, enlargement and metastasis of cancers. Their production of growth factors, chemokines and extracellular matrix facilitate the angiogenic recruitment of endothelial cells and pericytes. The oncogene Ras, known to be frequently mutated in many cancers, has also been shown to promote the expression of pro-angiogenic growth factors, chemokines and extracellular matrix components similar to those of fibroblasts. Here we show that mutant N-ras (N-rasm)/GFP - transduced NIH3T3 fibroblasts act to promote the ex vivo expansion of umbilical cord blood (UCB)-derived primitive endothelial progenitor cells through paracrine mechanisms. Biphasic expansion of both angiogenic and lymphangiogenic precursors was observed although they exhibited different dynamics in their expansion pattern. The first peak of expansion for both types of precursor cells was seen on day 10 with a 69-fold expansion of the CD34+VEGFR2+(endothelial) and a 23-fold expansion of CD34+VEGFR3+(lymphatic) cells co-cultured with media conditioned by N-rasm-transduced 3T3 cells. This compared to a 20-fold and 14-fold expansion respectively, in cells co-cultured with media conditioned by GFP (only)-transduced fibroblasts. Endothelial cell differentiation accounts for the dramatic reduction in the numbers of CD34+VEGFR2+ and CD34+VEGFR3+ precursor cells on day 14 with concomitant expansion of CD34−VEGFR2+ and CD34−VEGFR3+cells. The second peak for the expansion of endothelial precursor cells was seen on day 19 with a 214-fold expansion compared to 28-fold in the control cells. In addition, the expansion of CD14+ VEGFR2+ and CD14+VEGFR3+ cells was observed on days 14 and 19, the later correlated with the expansion of monocytic CD34−CD14+ cells promoted by N-rasm-transduced fibroblasts. The expanded monocytes appear to contribute to the expansion of endothelial and lymphatic precursor cells induced by N-rasm-transduced fibroblasts. We propose that the angiogenic factors secreted by mutant Ras-expressing fibroblasts in a tumour microenvironment promote tumour angiogenesis through the expansion of the circulated endothelial and lymphatic precursor cells. The recruitment of the expanded endothelial and lymphatic cells into the tumour’s vascular system is currently being investigated. We propose that targeting aberrant Ras signaling in tumour fibroblasts may represent an important target for cancer therapies.

The regulation of anoikis in tumor invasion and metastasis

2013 ◽  
Vol 35 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Hong SU ◽  
Xiao-Yu SI ◽  
Wen-Ru TANG ◽  
Ying LUO
Keyword(s):  
Tumor Invasion ◽  
Invasion And Metastasis

scholarly journals Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Satoshi Takagi ◽  
Yuki Sasaki ◽  
Sumie Koike ◽  
Ai Takemoto ◽  
Yosuke Seto ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Pulmonary Metastasis ◽  
Lysophosphatidic Acid ◽  
Therapeutic Intervention ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Osteosarcoma Cells ◽  
Invasion And Metastasis ◽  
Platelet Releasate

AbstractOsteosarcoma is the most common primary malignant bone cancer, with high rates of pulmonary metastasis. Osteosarcoma patients with pulmonary metastasis have worse prognosis than those with localized disease, leading to dramatically reduced survival rates. Therefore, understanding the biological characteristics of metastatic osteosarcoma and the molecular mechanisms of invasion and metastasis of osteosarcoma cells will lead to the development of innovative therapeutic intervention for advanced osteosarcoma. Here, we identified that osteosarcoma cells commonly exhibit high platelet activation-inducing characteristics, and molecules released from activated platelets promote the invasiveness of osteosarcoma cells. Given that heat-denatured platelet releasate maintained the ability to promote osteosarcoma invasion, we focused on heat-tolerant molecules, such as lipid mediators in the platelet releasate. Osteosarcoma-induced platelet activation leads to abundant lysophosphatidic acid (LPA) release. Exposure to LPA or platelet releasate induced morphological changes and increased invasiveness of osteosarcoma cells. By analyzing publicly available transcriptome datasets and our in-house osteosarcoma patient-derived xenograft tumors, we found that LPA receptor 1 (LPAR1) is notably upregulated in osteosarcoma. LPAR1 gene KO in osteosarcoma cells abolished the platelet-mediated osteosarcoma invasion in vitro and the formation of early pulmonary metastatic foci in experimental pulmonary metastasis models. Of note, the pharmacological inhibition of LPAR1 by the orally available LPAR1 antagonist, ONO-7300243, prevented pulmonary metastasis of osteosarcoma in the mouse models. These results indicate that the LPA–LPAR1 axis is essential for the osteosarcoma invasion and metastasis, and targeting LPAR1 would be a promising therapeutic intervention for advanced osteosarcoma.

scholarly journals The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eui Jung Moon ◽  
Stephano S. Mello ◽  
Caiyun G. Li ◽  
Jen-Tsan Chi ◽  
Kaushik Thakkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Invasion ◽  
Critical Role ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Invasion And Metastasis ◽  
Stat3 Signaling ◽  
Inducible Genes ◽  
Transcriptional Target

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.

IgG-recognizing shed tumor-associated antigens can promote tumor invasion and metastasis

2001 ◽  
Vol 50 (7) ◽  
pp. 361-372 ◽  
Author(s):  
Julie K. Nyhus ◽  
Chris C. Wolford ◽  
Chad R. Friece ◽  
Bud M. Nelson ◽  
James W. Sampsel ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Invasion And Metastasis ◽  
Tumor Associated Antigens
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