Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients

Eunjoo Hwang; Dong-Hyoung Lee; Ji-hyun Uh; Duyeol Han; Myoung Shin Kim; Sung Ho Choi; JooKyung Park; Byung Hee Jeon; Jinseon Lee; Se-Hoon Lee

doi:doi:10.11648/j.crj.20150301.13

| Peer-Reviewed |

Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients

Eunjoo Hwang, Dong-Hyoung Lee, Ji-hyun Uh, Duyeol Han, Myoung Shin Kim, Sung Ho Choi, JooKyung Park, Byung Hee Jeon, Jinseon Lee, Se-Hoon Lee

Received: 26 January 2015 Accepted: 14 February 2015 Published: 25 February 2015

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Circulating tumor cells (CTCs) are rare cells that have shed into the bloodstream from primary tumor, and potentiallyprovidea tool for the better understanding of tumor metastasis and noninvasive monitoring of the disease progression. However their isolation and characterization has been a major technological challenge due to their rareness. Here, we suggest the CTC culture as an effective method to obtain CTCs sufficient in numberfor molecular analysis of original tumor characteristics. We isolated and successfully cultured the CTCs from four lung cancer patients, and then analyzed those cells for ALK (anaplastic lymphoma kinase) fusion using real-time PCR method, and confirmed that the cultured CTCs have retained thefusion the same as those found in primary tumors. These results suggest that the isolation and culture of CTCs can be a substitutive method for tumor tissue biopsy, and may provide practically useful clinical applications, such as personalized cancer therapy based on their genomic information through serial blood samplings from the cancer patients.

DOI	10.11648/j.crj.20150301.13
Published in	Cancer Research Journal (Volume 3, Issue 1, January 2015)
Page(s)	11-16
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Lung Cancer, Circulating Tumor Cells, ALKRearrangement, Real Time PCR

References

[1]	Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, and Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med (2004) 351:781-91.
[2]	Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, Doyle GV, Tissing H, Terstappen LW, and Meropol NJ. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol (2008) 26:3213-21.
[3]	Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller MC, Fritsche HA, Hortobagyi GN, and Terstappen LW. Circulating tumor cells: A novel prognostic factor for newly diagnosed metastatic breaset cancer. J Clin Oncol (2005) 23:1420-30.
[4]	de Bono JS, Scher HI, Montgomery RB, Packer C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, and Raghavan D. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res (2008) 14:6302-9.
[5]	Haber DA, Gray NS, and Baselga J. The evolving waron cancer. Cell (2011) 145:19-24.
[6]	Yu M, Stott S, Toner M, Maheswaran S, and Haber DA. Circulating tumor cells: approaches to isolation and characterization. J Cell Biol (2011) 192:373-82.
[7]	Zer A and Leighl N. Promising targets and current clinical trials in metastatic non-squamous NSCLC. Front Oncol (2014) doi: 10.3389/fonc.2014.00329.
[8]	Faugeroux V, Pailler E, Auger N, Taylor M, and Farace F. Clinical utility of circulating tumor cells in ALK-positive non-small-cell lung cancer. Front Oncol (2014) doi: 10.3389/fonc.2014.00281.
[9]	Kim EH, Lee JK, Kim BC, Rhim SH, Kim JW, Kim KH, Jung SM, Park PS, Park HC, Lee J, and Jeon BH.Enrichment of cancer cells from wholeblood using a microfabricated porous filter.Anal Biochem (2013) 440:114-6.
[10]	Conde E, Angulo B, Izquierdo E, Muñoz L, Suárez-Gauthier A, Plaza C, Dominguez N, Torres M, Madrigal L, Rubio-Viqueira B, Belda-Iniesta C, Hidalgo M, López-Ríos F.The ALK translocation in advanced non-small-cell lung carcinomas: preapproval testing experience at a single cancer centre.Histopathology (2013) 62:609-16.
[11]	Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Stojanov P, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, and Haber DA. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science (2014) 345:216-20.
[12]	Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D, Goodman JC, Groves MD, and Marchetti D. The identification and characterization of breast cancer CTCs competent for brain metastasis.SciTransl Med (2013) 5:180ra48.
[13]	Tsuji T, Ibaragi S, Hu GF. Epithelial-mesenchymal transition and cell cooperativity in metastasis.Cancer Res (2009) 69:7135.
[14]	Armstrong AJ, Marengo MS, Otean S, Kemeny G, Bitting RL, Turnbull J, Herold CI, Marcom PK, Geroge D, and Garcia-Blanco MA. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res (2011) 9:997–1007.
[15]	He H, Yang X, Davidson AJ, Wu D, Marshall FF, Chung LW, Zhau HE, and Wang R.Progressive epithelial to mesenchymal transitions in ARCaPE prostate cancer cells during xenograft tumor formation and metastasis.Prostate (2010) 70:518-28.
[16]	Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, and Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.N Engl J Med (2010) 363:1693–703.
[17]	Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, and Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature (2007) 448:561–6.
[18]	Horn L and Pao W. EML4-ALK: honing in on a new target in non-small-cell lung cancer. J ClinOncol (2009) 27:4232–5.
[19]	Wang J, Cai Y, Dong Y, Nong J, Zhou L, Liu G, Su D, Li X, Wu S, Chen X, Qin N, Zeng X, Zhang H, Zhang Z, and Zhang S. Clinical characteristics and outcomes of patients with primary lung adenocarcinoma harboring ALK rearrangements detected by FISH, IHC, and RT-PCR. PLoS One(2014) 9(7):e101551.

Cite This Article

Plain Text BibTeX RIS

APA Style

Eunjoo Hwang, Dong-Hyoung Lee, Ji-hyun Uh, Duyeol Han, Myoung Shin Kim, et al. (2015). Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients. Cancer Research Journal, 3(1), 11-16. https://doi.org/10.11648/j.crj.20150301.13

Copy | Download

ACS Style

Eunjoo Hwang; Dong-Hyoung Lee; Ji-hyun Uh; Duyeol Han; Myoung Shin Kim, et al. Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients. Cancer Res. J. 2015, 3(1), 11-16. doi: 10.11648/j.crj.20150301.13

Copy | Download

AMA Style

Eunjoo Hwang, Dong-Hyoung Lee, Ji-hyun Uh, Duyeol Han, Myoung Shin Kim, et al. Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients. Cancer Res J. 2015;3(1):11-16. doi: 10.11648/j.crj.20150301.13

Copy | Download

@article{10.11648/j.crj.20150301.13,
  author = {Eunjoo Hwang and Dong-Hyoung Lee and Ji-hyun Uh and Duyeol Han and Myoung Shin Kim and Sung Ho Choi and JooKyung Park and Byung Hee Jeon and Jinseon Lee and Se-Hoon Lee},
  title = {Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients},
  journal = {Cancer Research Journal},
  volume = {3},
  number = {1},
  pages = {11-16},
  doi = {10.11648/j.crj.20150301.13},
  url = {https://doi.org/10.11648/j.crj.20150301.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20150301.13},
  abstract = {Circulating tumor cells (CTCs) are rare cells that have shed into the bloodstream from primary tumor, and potentiallyprovidea tool for the better understanding of tumor metastasis and noninvasive monitoring of the disease progression. However their isolation and characterization has been a major technological challenge due to their rareness. Here, we suggest the CTC culture as an effective method to obtain CTCs sufficient in numberfor molecular analysis of original tumor characteristics. We isolated and successfully cultured the CTCs from four lung cancer patients, and then analyzed those cells for ALK (anaplastic lymphoma kinase) fusion using real-time PCR method, and confirmed that the cultured CTCs have retained thefusion the same as those found in primary tumors.  These results suggest that the isolation and culture of CTCs can be a substitutive method for tumor tissue biopsy, and may provide practically useful clinical applications, such as personalized cancer therapy based on their genomic information through serial blood samplings from the cancer patients.},
 year = {2015}
}

Copy | Download

TY  - JOUR
T1  - Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients
AU  - Eunjoo Hwang
AU  - Dong-Hyoung Lee
AU  - Ji-hyun Uh
AU  - Duyeol Han
AU  - Myoung Shin Kim
AU  - Sung Ho Choi
AU  - JooKyung Park
AU  - Byung Hee Jeon
AU  - Jinseon Lee
AU  - Se-Hoon Lee
Y1  - 2015/02/25
PY  - 2015
N1  - https://doi.org/10.11648/j.crj.20150301.13
DO  - 10.11648/j.crj.20150301.13
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 11
EP  - 16
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20150301.13
AB  - Circulating tumor cells (CTCs) are rare cells that have shed into the bloodstream from primary tumor, and potentiallyprovidea tool for the better understanding of tumor metastasis and noninvasive monitoring of the disease progression. However their isolation and characterization has been a major technological challenge due to their rareness. Here, we suggest the CTC culture as an effective method to obtain CTCs sufficient in numberfor molecular analysis of original tumor characteristics. We isolated and successfully cultured the CTCs from four lung cancer patients, and then analyzed those cells for ALK (anaplastic lymphoma kinase) fusion using real-time PCR method, and confirmed that the cultured CTCs have retained thefusion the same as those found in primary tumors.  These results suggest that the isolation and culture of CTCs can be a substitutive method for tumor tissue biopsy, and may provide practically useful clinical applications, such as personalized cancer therapy based on their genomic information through serial blood samplings from the cancer patients.
VL  - 3
IS  - 1
ER  -

Copy | Download

Author Information

Eunjoo Hwang

Cytogen Inc., Seoul, Korea
Dong-Hyoung Lee

Cytogen Inc., Seoul, Korea
Ji-hyun Uh

Cytogen Inc., Seoul, Korea
Duyeol Han

Cytogen Inc., Seoul, Korea
Myoung Shin Kim

Cytogen Inc., Seoul, Korea
Sung Ho Choi

Cytogen Inc., Seoul, Korea
JooKyung Park

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Byung Hee Jeon

Cytogen Inc., Seoul, Korea
Jinseon Lee

Cytogen Inc., Seoul, Korea
Se-Hoon Lee

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Eunjoo Hwang, Dong-Hyoung Lee, Ji-hyun Uh, Duyeol Han, Myoung Shin Kim, et al. (2015). Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients. Cancer Research Journal, 3(1), 11-16. https://doi.org/10.11648/j.crj.20150301.13

Copy | Download

ACS Style

Eunjoo Hwang; Dong-Hyoung Lee; Ji-hyun Uh; Duyeol Han; Myoung Shin Kim, et al. Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients. Cancer Res. J. 2015, 3(1), 11-16. doi: 10.11648/j.crj.20150301.13

Copy | Download

AMA Style

Eunjoo Hwang, Dong-Hyoung Lee, Ji-hyun Uh, Duyeol Han, Myoung Shin Kim, et al. Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients. Cancer Res J. 2015;3(1):11-16. doi: 10.11648/j.crj.20150301.13

Copy | Download

@article{10.11648/j.crj.20150301.13,
  author = {Eunjoo Hwang and Dong-Hyoung Lee and Ji-hyun Uh and Duyeol Han and Myoung Shin Kim and Sung Ho Choi and JooKyung Park and Byung Hee Jeon and Jinseon Lee and Se-Hoon Lee},
  title = {Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients},
  journal = {Cancer Research Journal},
  volume = {3},
  number = {1},
  pages = {11-16},
  doi = {10.11648/j.crj.20150301.13},
  url = {https://doi.org/10.11648/j.crj.20150301.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20150301.13},
  abstract = {Circulating tumor cells (CTCs) are rare cells that have shed into the bloodstream from primary tumor, and potentiallyprovidea tool for the better understanding of tumor metastasis and noninvasive monitoring of the disease progression. However their isolation and characterization has been a major technological challenge due to their rareness. Here, we suggest the CTC culture as an effective method to obtain CTCs sufficient in numberfor molecular analysis of original tumor characteristics. We isolated and successfully cultured the CTCs from four lung cancer patients, and then analyzed those cells for ALK (anaplastic lymphoma kinase) fusion using real-time PCR method, and confirmed that the cultured CTCs have retained thefusion the same as those found in primary tumors.  These results suggest that the isolation and culture of CTCs can be a substitutive method for tumor tissue biopsy, and may provide practically useful clinical applications, such as personalized cancer therapy based on their genomic information through serial blood samplings from the cancer patients.},
 year = {2015}
}

Copy | Download

TY  - JOUR
T1  - Retaining ALK Rearrangement in Cultured Circulating Tumor Cells Derived from Lung Cancer Patients
AU  - Eunjoo Hwang
AU  - Dong-Hyoung Lee
AU  - Ji-hyun Uh
AU  - Duyeol Han
AU  - Myoung Shin Kim
AU  - Sung Ho Choi
AU  - JooKyung Park
AU  - Byung Hee Jeon
AU  - Jinseon Lee
AU  - Se-Hoon Lee
Y1  - 2015/02/25
PY  - 2015
N1  - https://doi.org/10.11648/j.crj.20150301.13
DO  - 10.11648/j.crj.20150301.13
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 11
EP  - 16
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20150301.13
AB  - Circulating tumor cells (CTCs) are rare cells that have shed into the bloodstream from primary tumor, and potentiallyprovidea tool for the better understanding of tumor metastasis and noninvasive monitoring of the disease progression. However their isolation and characterization has been a major technological challenge due to their rareness. Here, we suggest the CTC culture as an effective method to obtain CTCs sufficient in numberfor molecular analysis of original tumor characteristics. We isolated and successfully cultured the CTCs from four lung cancer patients, and then analyzed those cells for ALK (anaplastic lymphoma kinase) fusion using real-time PCR method, and confirmed that the cultured CTCs have retained thefusion the same as those found in primary tumors.  These results suggest that the isolation and culture of CTCs can be a substitutive method for tumor tissue biopsy, and may provide practically useful clinical applications, such as personalized cancer therapy based on their genomic information through serial blood samplings from the cancer patients.
VL  - 3
IS  - 1
ER  -

Copy | Download