Abstract
n-3 long chain Polyunsaturated Fatty Acids (n-3 LCPUFA) have been shown to improve the efficacy of conventional chemotherapies used for breast cancer treatment. In addition to their reported ability to increase the chemosensitivity of cancer cells, we hypothesized that n-3 LCPUFA could induce a remodeling of the vascular network in mammary tumors. A contrast-enhanced ultrasound method was used to monitor the vascular architecture during docetaxel treatment of mammary tumors in rats fed either a control or an n-3 LCPUFA-enriched diet (docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA)). The vascular network was remodeled in favor of smaller vessels (microvascularization), which represented 54% of the vasculature in n-3 LCPUFA tumors but only 26% in control tumors after 2 weeks of chemotherapy. Importantly, vascularization changes occurred both before and during docetaxel treatment. The density of smaller vessels quantified before chemotherapy was correlated with improved tumor size reduction by docetaxel treatment. Furthermore, transcript levels of the angiogenesis-specific genes epiregulin and amphiregulin were reduced by ~4.5- and twofold in tumors obtained from rats fed an n-3 LCPUFA-enriched diet compared to those of rats fed a control diet, respectively. Their expression levels were negatively correlated with tumor regression after chemotherapy. Taken together, this preclinical data strengthen the potential usefulness of n-3 LCPUFA as a complementary clinical strategy to improve drug efficiency via remodeling of the tumor vasculature.
Highlights
Unlike the normal vascular network, the tumor vascular tree lacks an orderly branched hierarchy from large vessels to successively smaller vessels that normally feed a capillary bed involved in the exchange of molecules such as oxygen, nutrients, or therapeutic agents
We previously reported that a reduction in the tumor vascularization during n-3 LCPUFA supplementation is accompanied by an enhancement of tumor sensitivity to anthracyclines or taxanes [8,12]
We show that, upon docetaxel treatment, the tumor vasculature with small caliber vessels remains preponderant in n-3 LCPUFA-tumors and is correlated with improved response to docetaxel chemotherapy
Summary
Unlike the normal vascular network, the tumor vascular tree lacks an orderly branched hierarchy from large vessels to successively smaller vessels (microvascularization) that normally feed a capillary bed involved in the exchange of molecules such as oxygen, nutrients, or therapeutic agents. Tumor vasculature quality is admittedly poorly developed, with highly dilated and permeable vessels leading to high interstitial fluid pressure. These differences can irreversibly affect the delivery of molecules and lead to poorly perfused regions within the tumor [1]. These types of structural abnormalities of the tumor vasculature have far-reaching consequences that include poor response to anticancer therapies. Vessels become smaller in diameter, less tortuous and are more efficient at delivering oxygen, nutrients, and drugs [2,3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
