Enhanced tumor cell isolation by a biomimetic combination of e-selectin and anti-epcam: Implications for the effective separation of circulating tumor cells (CTCs)

Ja Hye Myung, Cari A. Launiere, David T. Eddington, Seungpyo Hong

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The selective detection of circulating tumor cells (CTCs) is of significant clinical importance for the clinical diagnosis and prognosis of cancer metastasis. However, largely because of the extremely low number of CTCs (as low as 1 in 1.09 hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. Cell rolling is known to play a key role in physiological processes such as the recruitment of leukocytes to sites of inflammation and selectin-mediated CTC metastasis. Furthermore, because CTCs typically express the epithelial-cell, adhesion molecule (EpCAM) on the surface whereas normal hematologic cells do not, substrates with immobilized antibody against EpCAM may specifically interact with CTCs. In this article, we created biomimetic surfaces functionalized with P- and E-selectin and anti-EpCAM that induce different responses in HL-60 (used as a model of leukocytes in this study) and MCF-7 (a model of CTCs) cells. HL-60 and MCF-7 cells showed, different degrees of interaction with. P-/E-selectin and anti-EpCAM at a shear stress of 0.32 dyn/cm2. HL-60 cells exhibited rolling on P-selectin-immobilized substrates at a velocity of 2.26 ± 0.28 μm/s whereas MCF-7 cells had no interaction with the surface. Both cell lines, however, had interactions with E-selectin, and the rolling velocity of MCF-7 cells (4.24 ± 0.31 μm/s) was faster than that of HL-60 cells (2.12 ± 0.15 μm/s). However, only MCF-7 cells interacted with anti-EpCAM-coated, surfaces, forming stationary binding under flow. More importantly, the combination of the rolling (E-selectin) and stationary binding (anti-EpCAM) resulted in substantially enhanced separation capacity and capture efficiency (more than 3-fold enhancement), as compared to a surface functionalized solely with anti-EpCAM that has been commonly used for CTC capture. Our results indicate that cell-specific detection and separation may be achieved through mimicking the biological processes of combined dynamic cell, rolling and stationary binding, which will likely lead to a CTC detection device with significantly enhanced specificity and sensitivity without a complex fabrication process.

Original languageEnglish
Pages (from-to)8589-8596
Number of pages8
JournalLangmuir
Volume26
Issue number11
DOIs
Publication statusPublished - 2010 Jun 1

Fingerprint

Selectins
biomimetics
Biomimetics
Cell adhesion
Cell Adhesion Molecules
Tumors
isolation
tumors
Cells
E-Selectin
Molecules
cells
P-Selectin
adhesion
Immobilized Antibodies
Substrates
molecules
Epithelial Cells
Antibodies
leukocytes

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry

Cite this

@article{2e14a5f7829d4a4b9e75e04fab7cda38,
title = "Enhanced tumor cell isolation by a biomimetic combination of e-selectin and anti-epcam: Implications for the effective separation of circulating tumor cells (CTCs)",
abstract = "The selective detection of circulating tumor cells (CTCs) is of significant clinical importance for the clinical diagnosis and prognosis of cancer metastasis. However, largely because of the extremely low number of CTCs (as low as 1 in 1.09 hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. Cell rolling is known to play a key role in physiological processes such as the recruitment of leukocytes to sites of inflammation and selectin-mediated CTC metastasis. Furthermore, because CTCs typically express the epithelial-cell, adhesion molecule (EpCAM) on the surface whereas normal hematologic cells do not, substrates with immobilized antibody against EpCAM may specifically interact with CTCs. In this article, we created biomimetic surfaces functionalized with P- and E-selectin and anti-EpCAM that induce different responses in HL-60 (used as a model of leukocytes in this study) and MCF-7 (a model of CTCs) cells. HL-60 and MCF-7 cells showed, different degrees of interaction with. P-/E-selectin and anti-EpCAM at a shear stress of 0.32 dyn/cm2. HL-60 cells exhibited rolling on P-selectin-immobilized substrates at a velocity of 2.26 ± 0.28 μm/s whereas MCF-7 cells had no interaction with the surface. Both cell lines, however, had interactions with E-selectin, and the rolling velocity of MCF-7 cells (4.24 ± 0.31 μm/s) was faster than that of HL-60 cells (2.12 ± 0.15 μm/s). However, only MCF-7 cells interacted with anti-EpCAM-coated, surfaces, forming stationary binding under flow. More importantly, the combination of the rolling (E-selectin) and stationary binding (anti-EpCAM) resulted in substantially enhanced separation capacity and capture efficiency (more than 3-fold enhancement), as compared to a surface functionalized solely with anti-EpCAM that has been commonly used for CTC capture. Our results indicate that cell-specific detection and separation may be achieved through mimicking the biological processes of combined dynamic cell, rolling and stationary binding, which will likely lead to a CTC detection device with significantly enhanced specificity and sensitivity without a complex fabrication process.",
author = "Myung, {Ja Hye} and Launiere, {Cari A.} and Eddington, {David T.} and Seungpyo Hong",
year = "2010",
month = "6",
day = "1",
doi = "10.1021/la904678p",
language = "English",
volume = "26",
pages = "8589--8596",
journal = "Langmuir",
issn = "0743-7463",
publisher = "American Chemical Society",
number = "11",

}

Enhanced tumor cell isolation by a biomimetic combination of e-selectin and anti-epcam : Implications for the effective separation of circulating tumor cells (CTCs). / Myung, Ja Hye; Launiere, Cari A.; Eddington, David T.; Hong, Seungpyo.

In: Langmuir, Vol. 26, No. 11, 01.06.2010, p. 8589-8596.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhanced tumor cell isolation by a biomimetic combination of e-selectin and anti-epcam

T2 - Implications for the effective separation of circulating tumor cells (CTCs)

AU - Myung, Ja Hye

AU - Launiere, Cari A.

AU - Eddington, David T.

AU - Hong, Seungpyo

PY - 2010/6/1

Y1 - 2010/6/1

N2 - The selective detection of circulating tumor cells (CTCs) is of significant clinical importance for the clinical diagnosis and prognosis of cancer metastasis. However, largely because of the extremely low number of CTCs (as low as 1 in 1.09 hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. Cell rolling is known to play a key role in physiological processes such as the recruitment of leukocytes to sites of inflammation and selectin-mediated CTC metastasis. Furthermore, because CTCs typically express the epithelial-cell, adhesion molecule (EpCAM) on the surface whereas normal hematologic cells do not, substrates with immobilized antibody against EpCAM may specifically interact with CTCs. In this article, we created biomimetic surfaces functionalized with P- and E-selectin and anti-EpCAM that induce different responses in HL-60 (used as a model of leukocytes in this study) and MCF-7 (a model of CTCs) cells. HL-60 and MCF-7 cells showed, different degrees of interaction with. P-/E-selectin and anti-EpCAM at a shear stress of 0.32 dyn/cm2. HL-60 cells exhibited rolling on P-selectin-immobilized substrates at a velocity of 2.26 ± 0.28 μm/s whereas MCF-7 cells had no interaction with the surface. Both cell lines, however, had interactions with E-selectin, and the rolling velocity of MCF-7 cells (4.24 ± 0.31 μm/s) was faster than that of HL-60 cells (2.12 ± 0.15 μm/s). However, only MCF-7 cells interacted with anti-EpCAM-coated, surfaces, forming stationary binding under flow. More importantly, the combination of the rolling (E-selectin) and stationary binding (anti-EpCAM) resulted in substantially enhanced separation capacity and capture efficiency (more than 3-fold enhancement), as compared to a surface functionalized solely with anti-EpCAM that has been commonly used for CTC capture. Our results indicate that cell-specific detection and separation may be achieved through mimicking the biological processes of combined dynamic cell, rolling and stationary binding, which will likely lead to a CTC detection device with significantly enhanced specificity and sensitivity without a complex fabrication process.

AB - The selective detection of circulating tumor cells (CTCs) is of significant clinical importance for the clinical diagnosis and prognosis of cancer metastasis. However, largely because of the extremely low number of CTCs (as low as 1 in 1.09 hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. Cell rolling is known to play a key role in physiological processes such as the recruitment of leukocytes to sites of inflammation and selectin-mediated CTC metastasis. Furthermore, because CTCs typically express the epithelial-cell, adhesion molecule (EpCAM) on the surface whereas normal hematologic cells do not, substrates with immobilized antibody against EpCAM may specifically interact with CTCs. In this article, we created biomimetic surfaces functionalized with P- and E-selectin and anti-EpCAM that induce different responses in HL-60 (used as a model of leukocytes in this study) and MCF-7 (a model of CTCs) cells. HL-60 and MCF-7 cells showed, different degrees of interaction with. P-/E-selectin and anti-EpCAM at a shear stress of 0.32 dyn/cm2. HL-60 cells exhibited rolling on P-selectin-immobilized substrates at a velocity of 2.26 ± 0.28 μm/s whereas MCF-7 cells had no interaction with the surface. Both cell lines, however, had interactions with E-selectin, and the rolling velocity of MCF-7 cells (4.24 ± 0.31 μm/s) was faster than that of HL-60 cells (2.12 ± 0.15 μm/s). However, only MCF-7 cells interacted with anti-EpCAM-coated, surfaces, forming stationary binding under flow. More importantly, the combination of the rolling (E-selectin) and stationary binding (anti-EpCAM) resulted in substantially enhanced separation capacity and capture efficiency (more than 3-fold enhancement), as compared to a surface functionalized solely with anti-EpCAM that has been commonly used for CTC capture. Our results indicate that cell-specific detection and separation may be achieved through mimicking the biological processes of combined dynamic cell, rolling and stationary binding, which will likely lead to a CTC detection device with significantly enhanced specificity and sensitivity without a complex fabrication process.

UR - http://www.scopus.com/inward/record.url?scp=77954549013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954549013&partnerID=8YFLogxK

U2 - 10.1021/la904678p

DO - 10.1021/la904678p

M3 - Article

C2 - 20155985

AN - SCOPUS:77954549013

VL - 26

SP - 8589

EP - 8596

JO - Langmuir

JF - Langmuir

SN - 0743-7463

IS - 11

ER -