Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Feb 3:13:9.
doi: 10.1186/s12951-015-0072-x.

Exploring cancer metastasis prevention strategy: interrupting adhesion of cancer cells to vascular endothelia of potential metastatic tissues by antibody-coated nanomaterial

Jingjing Xie  1 , Haiyan Dong  2 , Hongning Chen  3 , Rongli Zhao  4 , Patrick J Sinko  5 , Weiyu Shen  6 , Jichuang Wang  7 , Yusheng Lu  8 , Xiang Yang  9 , Fangwei Xie  10 , Lee Jia  11
Affiliations

Exploring cancer metastasis prevention strategy: interrupting adhesion of cancer cells to vascular endothelia of potential metastatic tissues by antibody-coated nanomaterial

Jingjing Xie et al. J Nanobiotechnology. .

Abstract

Background: Cancer metastasis caused by circulating tumor cells (CTCs) accounts for 90% cancer-related death worldwide. Blocking the circulation of CTCs in bloodstream and their hetero-adhesion to vascular endothelia of the distant metastatic organs may prevent cancer metastasis. Nanomaterial-based intervention with adhesion between CTCs and endothelia has not been reported. Driven by the novel idea that multivalent conjugation of EpCAM and Slex antibodies to dendrimer surface may enhance the capacity and specificity of the nanomaterial conjugates for capturing and down-regulating colorectal CTCs, we conjugated the dendrimer nanomaterial with the EpCAM and Slex antibodies, and examined the capacity of the dual antibody-coated nanomaterial for their roles in interrupting CTCs-related cancer metastasis.

Results: The antibody-coated nanomaterial was synthesized and characterized. The conjugates specifically bound and captured colon cancer cells SW620. The conjugate inhibited the cells' viability and their adhesion to fibronectin (Fn)-coated substrate or human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. In comparison with SW480 and LoVo cell lines, the activity and adhesion of SW620 to Fn-coated substrate and HUVECs were more specifically inhibited by the dual antibody conjugate because of the higher levels of EpCAM and Slex on SW620 cell surface. The hetero-adhesion between SW620 and Fn-coated substrate, or HUVECs was inhibited by about 60-70%. The dual conjugate showed the inhibition capacity more significant than its corresponding single antibody conjugates.

Conclusions: The present study provides the new evidence that coating nanomaterials with more than one antibody against CTCs may effectively interfere with the interaction between SW620 and HUVECs.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Synthesis and physiochemical characterization of dendrimers assembling with antiEpCAM and antiSlex with or without fluorescence labeling. a, Schematic illustration of the construction of dual antibody-conjugated dendrimers for exploring their biological functions in cancer metastasis through binding the target cancer cells. b, Images of PE-5A-G6-5S-FITC conjugate in aqueous solution under a laser confocal microscope. c, A FSEM image of the dry conjugate G6-5A-5S. d, The ultraviolet absorption spectra of CC G6 dendrimers, antibody and dual antibody conjugates in PBS (pH 7.4) solution.
Figure 2
Figure 2
Fluorescence micrographs of the adherent colon cancer cell lines (SW620, SW480 and LoVo) respectively bound by PE-5A-G6-5S-FITC conjugate at various concentrations (0, 10, 20 μg mL −1 ). Cell nucleus was stained with blue color (positive to DAPI) while cell membrane was labeled with the merged yellow-green color (positive to both FITC and PE).
Figure 3
Figure 3
Qualitative and quantitative analyses of the suspensory SW620 and LoVo cell lines respectively captured by PE-5A-G6-5S-FITC conjugate at the same concentration of 20 μg mL −1 . a, Representative fluorescence images of the captured cell lines at different excitation channels. b, Flow cytometric analysis of the capture efficiency of the conjugate in comparison with the isotype control.
Figure 4
Figure 4
Decrease in viability of colon cancer cell lines induced by single and dual antibody conjugates at concentrations ranging from 1.25 to 20 μg mL −1 . a, SW480 cells; b, LoVo cells; c, SW620 cells.
Figure 5
Figure 5
Cell cycle distribution and cellular MMP of colon cancer cell lines after exposure to dual antibody conjugate G6-5A-5S at 10 and 20 μg mL −1 . a, DNA flow cytometric images of the treated SW620 cells with the conjugate. b, Percentage of cell population in every stage (G0/G1, S and G2/M). c, The influence of conjugate on the cellular MMP. The increased fluorescence intensity of DiOC6(3) usually indicated the decreased MMP.
Figure 6
Figure 6
The concentration-dependent inhibition of single and dual antibody conjugates (from 1.25 to 10 μg mL −1 ) on the adhesion of colon cancer cell lines to Fn-coated substrate. a, SW480 cells; b, LoVo cells; c, SW620 cells.
Figure 7
Figure 7
Inhibition by single and dual antibody conjugates on the hetero-adhesion between colon cancer cell lines and HUVECs concentration-dependently (1.25 to 10 μg mL −1 ). a-c, The conjugates showed the different capability in interfering with the adhesion of cancer cell lines to HUVECs. a, LoVo cells; b, SW480 cells; c, SW620 cells. d, Representative fluorescence images of Rhodamine 123-labeled SW480 cells that adhered to HUVECs when they were treated with different concentrations of G6-5A-5S conjugate.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81. doi: 10.1016/j.ejca.2009.12.014. - DOI - PubMed
    1. Bach PB. Costs of cancer care: a view from the centers for Medicare and Medicaid services. J Clin Oncol. 2007;25:187–90. doi: 10.1200/JCO.2006.08.6116. - DOI - PubMed
    1. Sethi N, Kang Y. Unravelling the complexity of metastasis - molecular understanding and targeted therapies. Nat Rev Cancer. 2011;11:735–48. doi: 10.1038/nrc3125. - DOI - PMC - PubMed
    1. Klein CA. Cancer. The metastasis cascade. Science. 2008;321:1785–7. doi: 10.1126/science.1164853. - DOI - PubMed
    1. Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12:895–904. doi: 10.1038/nm1469. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources