Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells

Tsai Mu Cheng, Yanal M. Murad, Chia Ching Chang, Ming Chi Yang, Toya Nath Baral, Aaron Cowan, Shin Hua Tseng, Andrew Wong, Roger Mackenzie, Dar Bin Shieh, Jianbing Zhang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is over-expressed in pancreatic cancer cells, and it is associated with the progression of pancreatic cancer. We tested a single domain antibody (sdAb) targeting CEACAM6, 2A3, which was isolated previously from a llama immune library, and an Fc conjugated version of this sdAb, to determine how they affect the pancreatic cancer cell line BxPC3. We also compared the effects of the antibodies to gemcitabine. Gemcitabine and 2A3 slowed down cancer cell proliferation. However, only 2A3 retarded cancer cell invasion, angiogenesis within the cancer mass and BxPC3 cell MMP-9 activity, three features important for tumour growth and metastasis. The IC50s for 2A3, 2A3-Fc and gemcitabine were determined as 6.5 μM, 8 μM and 12 nM, respectively. While the 2A3 antibody inhibited MMP-9 activity by 33% compared to non-treated control cells, gemcitabine failed to inhibit MMP-9 activity. Moreover, 2A3 and 2A3-Fc inhibited invasion of BxPC3 by 73% compared to non-treated cells. When conditioned media that were produced using 2A3- or 2A3-Fc-treated BxPC3 cells were used in a capillary formation assay, the capillary length was reduced by 21% and 49%, respectively. Therefore 2A3 is an ideal candidate for treating tumours that over-express CEACAM6.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalEuropean Journal of Cancer
Volume50
Issue number4
DOIs
Publication statusPublished - Mar 2014
Externally publishedYes

Fingerprint

Single-Domain Antibodies
gemcitabine
Carcinoembryonic Antigen
Cell Adhesion Molecules
Pancreatic Neoplasms
Matrix Metalloproteinases
Neoplasms
New World Camelids
Antibodies
Conditioned Culture Medium
Libraries
Cell Proliferation
Neoplasm Metastasis
Cell Line
Growth

Keywords

  • Angiogenesis
  • BxPC3
  • CEACAM6
  • Gemcitabine
  • MMP-9
  • Pancreatic cancer
  • Single domain antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells. / Cheng, Tsai Mu; Murad, Yanal M.; Chang, Chia Ching; Yang, Ming Chi; Baral, Toya Nath; Cowan, Aaron; Tseng, Shin Hua; Wong, Andrew; Mackenzie, Roger; Shieh, Dar Bin; Zhang, Jianbing.

In: European Journal of Cancer, Vol. 50, No. 4, 03.2014, p. 713-721.

Research output: Contribution to journalArticle

Cheng, Tsai Mu ; Murad, Yanal M. ; Chang, Chia Ching ; Yang, Ming Chi ; Baral, Toya Nath ; Cowan, Aaron ; Tseng, Shin Hua ; Wong, Andrew ; Mackenzie, Roger ; Shieh, Dar Bin ; Zhang, Jianbing. / Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells. In: European Journal of Cancer. 2014 ; Vol. 50, No. 4. pp. 713-721.
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abstract = "Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is over-expressed in pancreatic cancer cells, and it is associated with the progression of pancreatic cancer. We tested a single domain antibody (sdAb) targeting CEACAM6, 2A3, which was isolated previously from a llama immune library, and an Fc conjugated version of this sdAb, to determine how they affect the pancreatic cancer cell line BxPC3. We also compared the effects of the antibodies to gemcitabine. Gemcitabine and 2A3 slowed down cancer cell proliferation. However, only 2A3 retarded cancer cell invasion, angiogenesis within the cancer mass and BxPC3 cell MMP-9 activity, three features important for tumour growth and metastasis. The IC50s for 2A3, 2A3-Fc and gemcitabine were determined as 6.5 μM, 8 μM and 12 nM, respectively. While the 2A3 antibody inhibited MMP-9 activity by 33{\%} compared to non-treated control cells, gemcitabine failed to inhibit MMP-9 activity. Moreover, 2A3 and 2A3-Fc inhibited invasion of BxPC3 by 73{\%} compared to non-treated cells. When conditioned media that were produced using 2A3- or 2A3-Fc-treated BxPC3 cells were used in a capillary formation assay, the capillary length was reduced by 21{\%} and 49{\%}, respectively. Therefore 2A3 is an ideal candidate for treating tumours that over-express CEACAM6.",
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AU - Yang, Ming Chi

AU - Baral, Toya Nath

AU - Cowan, Aaron

AU - Tseng, Shin Hua

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AU - Mackenzie, Roger

AU - Shieh, Dar Bin

AU - Zhang, Jianbing

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AB - Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is over-expressed in pancreatic cancer cells, and it is associated with the progression of pancreatic cancer. We tested a single domain antibody (sdAb) targeting CEACAM6, 2A3, which was isolated previously from a llama immune library, and an Fc conjugated version of this sdAb, to determine how they affect the pancreatic cancer cell line BxPC3. We also compared the effects of the antibodies to gemcitabine. Gemcitabine and 2A3 slowed down cancer cell proliferation. However, only 2A3 retarded cancer cell invasion, angiogenesis within the cancer mass and BxPC3 cell MMP-9 activity, three features important for tumour growth and metastasis. The IC50s for 2A3, 2A3-Fc and gemcitabine were determined as 6.5 μM, 8 μM and 12 nM, respectively. While the 2A3 antibody inhibited MMP-9 activity by 33% compared to non-treated control cells, gemcitabine failed to inhibit MMP-9 activity. Moreover, 2A3 and 2A3-Fc inhibited invasion of BxPC3 by 73% compared to non-treated cells. When conditioned media that were produced using 2A3- or 2A3-Fc-treated BxPC3 cells were used in a capillary formation assay, the capillary length was reduced by 21% and 49%, respectively. Therefore 2A3 is an ideal candidate for treating tumours that over-express CEACAM6.

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