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MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that has important roles in angiogenesis. Our knowledge of the significance of VEGF isoforms in human cancer remains incomplete.

Methods:: Bioluminescence imaging and transcriptomic analysis were used to study the colonisation capacity of the human breast cancer cells MDA-MB-231 controlling or overexpressing the VEGF165 or VEGF189 isoform (named cV-B, V165-B and V189-B, respectively) in nude mice.

Results:: When injected into the bloodstream, V189-B cells induced less metastasis in the lungs and bone than V165-B and cV-B control cells, consistent with longer survival of these mice and delay in tumour uptake in the mice injected with a V189-B clone. Histological analysis confirmed that there were less αSMA-positive cells in the lungs of the mice injected with V189-B. In vitro V189-B cells decreased both cell invasion and survival. Using transcriptomic analysis, we identified a subset of 18 genes expressed differentially between V189 and V165 cell lines and in 120 human breast tumours. V165 was associated with poor prognosis, whereas V189 was not, suggesting a complex regulation by VEGF isoforms. Our results showed a negative correlation between the expression pattern of VEGF189 and the levels of expression of seven genes that influence metastasis.

Conclusion:: Our findings provide the first evidence that VEGF isoforms have different effects on breast cancer cell line colonisation in vivo.

No MeSH data available.


In silico analysis protocol. (A) In silico analysis comparing V165 with V189 as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165 with V189. (B) In silico analysis comparing V165M with V189M as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165M with V189M.
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fig4: In silico analysis protocol. (A) In silico analysis comparing V165 with V189 as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165 with V189. (B) In silico analysis comparing V165M with V189M as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165M with V189M.

Mentions: We compared the transcriptomic profiles of the V165 and V189 cell lines (Supplementary Data S4). We identified a subset of 149 genes with significantly different expression levels in the two cell lines (V165 vs V189) (P<0.05 and /Log FC/>1) (Supplementary Data S4). We reduced the number of genes for further analysis, by comparing our 149 deregulated genes with a list of human genes known to be specifically involved in mammary carcinogenesis. We used the Richardson breast 2 database (oncomine.org), which compared the expression of 19 514 human genes between 40 breast tumours and seven normal breast tissue samples. We found that 36 genes expressed differentially between V165 and V189 cells (V165 vs V189 list) were also included in the Richardson breast 2 database (Figure 4A). We then analysed the expression profiles of the 36 genes identified with BRB-ArrayTools and a metastasis potential event selection filter, and identified 11 genes expressed significantly (Figure 4A).


MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics
In silico analysis protocol. (A) In silico analysis comparing V165 with V189 as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165 with V189. (B) In silico analysis comparing V165M with V189M as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165M with V189M.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559830&req=5

fig4: In silico analysis protocol. (A) In silico analysis comparing V165 with V189 as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165 with V189. (B) In silico analysis comparing V165M with V189M as described in Materials and methods, and genes significantly expressed in the BRB data set and associated with invasive potential in the comparison of V165M with V189M.
Mentions: We compared the transcriptomic profiles of the V165 and V189 cell lines (Supplementary Data S4). We identified a subset of 149 genes with significantly different expression levels in the two cell lines (V165 vs V189) (P<0.05 and /Log FC/>1) (Supplementary Data S4). We reduced the number of genes for further analysis, by comparing our 149 deregulated genes with a list of human genes known to be specifically involved in mammary carcinogenesis. We used the Richardson breast 2 database (oncomine.org), which compared the expression of 19 514 human genes between 40 breast tumours and seven normal breast tissue samples. We found that 36 genes expressed differentially between V165 and V189 cells (V165 vs V189 list) were also included in the Richardson breast 2 database (Figure 4A). We then analysed the expression profiles of the 36 genes identified with BRB-ArrayTools and a metastasis potential event selection filter, and identified 11 genes expressed significantly (Figure 4A).

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that has important roles in angiogenesis. Our knowledge of the significance of VEGF isoforms in human cancer remains incomplete.

Methods:: Bioluminescence imaging and transcriptomic analysis were used to study the colonisation capacity of the human breast cancer cells MDA-MB-231 controlling or overexpressing the VEGF165 or VEGF189 isoform (named cV-B, V165-B and V189-B, respectively) in nude mice.

Results:: When injected into the bloodstream, V189-B cells induced less metastasis in the lungs and bone than V165-B and cV-B control cells, consistent with longer survival of these mice and delay in tumour uptake in the mice injected with a V189-B clone. Histological analysis confirmed that there were less &alpha;SMA-positive cells in the lungs of the mice injected with V189-B. In vitro V189-B cells decreased both cell invasion and survival. Using transcriptomic analysis, we identified a subset of 18 genes expressed differentially between V189 and V165 cell lines and in 120 human breast tumours. V165 was associated with poor prognosis, whereas V189 was not, suggesting a complex regulation by VEGF isoforms. Our results showed a negative correlation between the expression pattern of VEGF189 and the levels of expression of seven genes that influence metastasis.

Conclusion:: Our findings provide the first evidence that VEGF isoforms have different effects on breast cancer cell line colonisation in vivo.

No MeSH data available.