Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 3/2015

01-03-2015 | Research Article

A549 cells adapted to high nitric oxide show reduced surface CEACAM expression and altered adhesion and migration properties

Authors: Madeeha Aqil, Kim M. Elseth, Ashok Arjunakani, Philip Nebres, Courtney P. Amegashie, Devang H. Thanki, Premal B. Desai, James A. Radosevich

Published in: Tumor Biology | Issue 3/2015

Login to get access

Abstract

The migration and adhesion properties of tumors affect their metastatic rate. In the present study, we investigated carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 1, 5, and 6 expression in high nitric oxide (HNO)-adapted lung cancer cells compared to parent cells. We observed high transcript levels of CEACAM 1 (4S, 4L), CEACAM 5, and CEACAM 6 in HNO cells compared to parent cells. However, the surface expression was low in HNO cells. Interestingly, the intracellular protein levels were high for these three CEACAMs. We confirmed these results with immunohistochemical experiments. Further, the adhesion and migration assays showed reduced clumping in HNO-adapted A549 (A549-HNO) cells and faster migration rates, respectively. These results document the altered adhesion and migration properties of cells adapted to HNO. Further, our studies also indicate a dynamic regulation of CEACAM protein expression and surface transport in HNO cells.
Literature
1.
Beauchemin N, Arabzadeh A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013;32(3–4):643–71.CrossRefPubMed
2.
3.
Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9(2):67–81.CrossRefPubMed
4.
Kodera Y, Isobe K, Yamauchi M, Satta T, Hasegawa T, Oikawa S, et al. Expression of carcinoembryonic antigen (CEA) and nonspecific crossreacting antigen (NCA) in gastrointestinal cancer; the correlation with degree of differentiation. Br J Cancer. 1993;68(1):130–6.CrossRefPubMedPubMedCentral
5.
Wirth T, Soeth E, Czubayko F, Juhl H. Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth. Clin Exp Metastasis. 2002;19(2):155–60.CrossRefPubMed
6.
Gemei M, Mirabelli P, Di Noto R, Corbo C, Iaccarino A, Zamboli A, et al. CD66c is a novel marker for colorectal cancer stem cell isolation, and its silencing halts tumor growth in vivo. Cancer. 2013;119(4):729–38.CrossRefPubMed
7.
Witzens-Harig M, Hose D, Junger S, Pfirschke C, Khandelwal N, Umansky L, et al. Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6. Blood. 2013;121(22):4493–503.CrossRefPubMed
8.
Tsang JY, Kwok YK, Chan KW, Ni YB, Chow WN, Lau KF, et al. Expression and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 6 in breast cancers. Breast Cancer Res Treat. 2013;142(2):311–22.CrossRefPubMed
9.
10.
Laack E, Nikbakht H, Peters A, Kugler C, Jasiewicz Y, Edler L, et al. Expression of CEACAM1 in adenocarcinoma of the lung: a factor of independent prognostic significance. J Clin Oncol. 2002;20(21):4279–84.CrossRefPubMed
11.
Thies A, Moll I, Berger J, Wagener C, Brummer J, Schulze HJ, et al. CEACAM1 expression in cutaneous malignant melanoma predicts the development of metastatic disease. J Clin Oncol. 2002;20(10):2530–6.CrossRefPubMed
12.
Toffalorio F, Belloni E, Barberis M, Bucci G, Tizzoni L, Pruneri G, et al. Gene expression profiling reveals GC and CEACAM1 as new tools in the diagnosis of lung carcinoids. Br J Cancer. 2014;110(5):1244–9.CrossRefPubMedPubMedCentral
13.
Kuespert K, Pils S, Hauck CR. CEACAMs: their role in physiology and pathophysiology. Curr Opin Cell Biol. 2006;18(5):565–71.CrossRefPubMed
14.
Vesper BJ, Elseth KM, Tarjan G, Haines 3rd GK, Radosevich JA. Long-term adaptation of lung tumor cell lines with increasing concentrations of nitric oxide donor. The Open Lung Cancer J. 2009;2:35–44.CrossRef
15.
Bentz BG, Simmons RL, Haines 3rd GK, Radosevich JA. The yin and yang of nitric oxide: reflections on the physiology and pathophysiology of NO. Head Neck. 2000;22(1):71–83.CrossRefPubMed
16.
Bentz BG, Hammer ND, Radosevich JA, Haines 3rd GK. Nitrosative stress induces DNA strand breaks but not caspase mediated apoptosis in a lung cancer cell line. J Carcinog. 2004;3(1):16.CrossRefPubMedPubMedCentral
17.
Aqil M, Elseth KM, Vesper BJ, Deliu Z, Aydogan B, Xue J, et al. Part I—mechanism of adaptation: high nitric oxide adapted A549 cells show enhanced DNA damage response and activation of antiapoptotic pathways. Tumour Biol. 2014;35(3):2403–15.CrossRefPubMed
18.
Aqil M, Deliu Z, Elseth KM, Shen G, Xue J, Radosevich JA. Part II—mechanism of adaptation: A549 cells adapt to high concentration of nitric oxide through bypass of cell cycle checkpoints. Tumour Biol. 2014;35(3):2417–25.CrossRefPubMed
19.
Paradise WA, Vesper BJ, Goel A, Waltonen JD, Altman KW, Haines GK, et al. Nitric oxide: perspectives and emerging studies of a well known cytotoxin. Int J Mol Sci. 2010;11(7):2715–45.CrossRefPubMedPubMedCentral
20.
Bentz BG, Hammer ND, Milash B, Klein S, Burnett DM, Radosevich JA, et al. The kinetics and redox state of nitric oxide determine the biological consequences in lung adenocarcinoma. Tumour Biol. 2007;28(6):301–11.CrossRefPubMed
21.
Cubillos-Rojas M, Amair-Pinedo F, Tato I, Bartrons R, Ventura F, Rosa JL. Simultaneous electrophoretic analysis of proteins of very high and low molecular mass using Tris-acetate polyacrylamide gels. Electrophoresis. 31(8):1318–21.
22.
Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2(2):329–33.CrossRefPubMed
23.
Sienel W, Dango S, Woelfle U, Morresi-Hauf A, Wagener C, Brummer J, et al. Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 promotes progression of non-small cell lung cancer. Clin Cancer Res. 2003;9(6):2260–6.PubMed
24.
Singer BB, Scheffrahn I, Kammerer R, Suttorp N, Ergun S, Slevogt H. Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells. PLoS One. 2010;5(1):e8747.CrossRefPubMedPubMedCentral
25.
Muturi HT, Dreesen JD, Nilewski E, Jastrow H, Giebel B, Ergun S, et al. Tumor and endothelial cell-derived microvesicles carry distinct CEACAMs and influence T-cell behavior. PLoS One. 2013;8(9):e74654.CrossRefPubMedPubMedCentral
26.
Davis FM, Stewart TA, Thompson EW, Monteith GR. Targeting EMT in cancer: opportunities for pharmacological intervention. Trends Pharmacol Sci. 2014.
27.
De Sanctis F, Sandri S, Ferrarini G, Pagliarello I, Sartoris S, Ugel S, et al. The emerging immunological role of post-translational modifications by reactive nitrogen species in cancer microenvironment. Front Immunol. 2014;5:69.CrossRefPubMedPubMedCentral
28.
Vesper BJ, Onul A, Haines 3rd GK, Tarjan G, Xue J, Elseth KM, et al. Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines. Tumour Biol. 2013;34(1):203–14.CrossRefPubMed
29.
De Vitto H, Mendonca BS, Elseth KM, Vesper BJ, Portari EA, Gallo CV, et al. Part II. Mitochondrial mutational status of high nitric oxide adapted cell line BT-20 (BT-20-HNO) as it relates to human primary breast tumors. Tumour Biol. 2013;34(1):337–47.CrossRefPubMed
30.
De Vitto H, Mendonca BS, Elseth KM, Onul A, Xue J, Vesper BJ, et al. Part III. Molecular changes induced by high nitric oxide adaptation in human breast cancer cell line BT-20 (BT-20-HNO): a switch from aerobic to anaerobic metabolism. Tumour Biol. 2013;34(1):403–13.CrossRefPubMed
31.
Onul A, Elseth KM, De Vitto H, Paradise WA, Vesper BJ, Tarjan G, et al. Long-term adaptation of the human lung tumor cell line A549 to increasing concentrations of hydrogen peroxide. Tumour Biol. 2012;33(3):739–48.CrossRefPubMed
32.
Yarmolyuk YR, Vesper BJ, Paradise WA, Elseth KM, Tarjan G, Haines 3rd GK, et al. Part I. Development of a model system for studying nitric oxide in tumors: high nitric oxide-adapted head and neck squamous cell carcinoma cell lines. Tumour Biol. 2011;32(1):77–85.CrossRefPubMed
33.
Tarjan G, Haines 3rd GK, Vesper BJ, Xue J, Altman MB, Yarmolyuk YR, et al. Part II. Initial molecular and cellular characterization of high nitric oxide-adapted human tongue squamous cell carcinoma cell lines. Tumour Biol. 2011;32(1):87–98.CrossRefPubMed
34.
Vesper BJ, Elseth KM, Tarjan G, Haines 3rd GK, Radosevich JA. Long-term adaptation of breast tumor cell lines to high concentrations of nitric oxide. Tumour Biol. 2010;31(4):267–75.CrossRefPubMed
35.
Bentz BG, Chandra R, Haines 3rd GK, Robinson AM, Shah P, Radosevich JA. Nitric oxide and apoptosis during human head and neck squamous cell carcinoma development. Am J Otolaryngol. 2002;23(1):4–11.CrossRefPubMed
36.
Chandra R, Haines 3rd GK, Bentz BG, Shah P, Robinson AM, Radosevich JA. Expression of nitric oxide synthase type 3 in reflux-induced esophageal lesions. Otolaryngol Head Neck Surg. 2001;124(4):442–7.CrossRefPubMed
37.
Bentz BG, Haines 3rd GK, Radosevich JA. Increased protein nitrosylation in head and neck squamous cell carcinogenesis. Head Neck. 2000;22(1):64–70.CrossRefPubMed
38.
Bentz BG, Haines 3rd GK, Lingen MW, Pelzer HJ, Hanson DG, Radosevich JA. Nitric oxide synthase type 3 is increased in squamous hyperplasia, dysplasia, and squamous cell carcinoma of the head and neck. Ann Otol Rhinol Laryngol. 1999;108(8):781–7.CrossRefPubMed
39.
Bentz BG, Haines 3rd GK, Hanson DG, Radosevich JA. Endothelial constitutive nitric oxide synthase (ecNOS) localization in normal and neoplastic salivary tissue. Head Neck. 1998;20(4):304–9.CrossRefPubMed
40.
Zhang L, Liu J, Wang X, Li Z, Zhang X, Cao P, et al. Upregulation of cytoskeleton protein and extracellular matrix protein induced by stromal-derived nitric oxide promotes lung cancer invasion and metastasis. Curr Mol Med. 2014.
41.
42.
Lawson EL, Mills DR, Brilliant KE, Hixson DC. The transmembrane domain of CEACAM1-4S is a determinant of anchorage independent growth and tumorigenicity. PLoS One. 2012;7(1):e29606.CrossRefPubMedPubMedCentral
43.
Kobayashi M, Miki Y, Ebina M, Abe K, Mori K, Narumi S, et al. Carcinoembryonic antigen-related cell adhesion molecules as surrogate markers for EGFR inhibitor sensitivity in human lung adenocarcinoma. Br J Cancer. 2012;107(10):1745–53.CrossRefPubMedPubMedCentral
44.
Strickland LA, Ross J, Williams S, Ross S, Romero M, Spencer S, et al. Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma. J Pathol. 2009;218(3):380–90.CrossRefPubMed
45.
Han SU, Kwak TH, Her KH, Cho YH, Choi C, Lee HJ, et al. CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling. Oncogene. 2008;27(5):675–83.CrossRefPubMed
46.
Hokari M, Matsuda Y, Wakai T, Shirai Y, Sato M, Tsuchiya A, et al. Tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 potentates the anchorage-independent growth of human hepatoma HepG2 cells. Life Sci. 2007;81(4):336–45.CrossRefPubMed
47.
Dango S, Sienel W, Schreiber M, Stremmel C, Kirschbaum A, Pantel K, et al. Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) is associated with increased angiogenic potential in non-small-cell lung cancer. Lung Cancer. 2008;60(3):426–33.CrossRefPubMed
48.
Liu W, Wei W, Winer D, Bamberger AM, Bamberger C, Wagener C, et al. CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases. Oncogene. 2007;26(19):2747–58.CrossRefPubMed
49.
Dery KJ, Gaur S, Gencheva M, Yen Y, Shively JE, Gaur RK. Mechanistic control of carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) splice isoforms by the heterogeneous nuclear ribonuclear proteins hnRNP L, hnRNP A1, and hnRNP M. J Biol Chem. 2011;286(18):16039–51.CrossRefPubMedPubMedCentral
50.
Singer BB, Scheffrahn I, Heymann R, Sigmundsson K, Kammerer R, Obrink B. Carcinoembryonic antigen-related cell adhesion molecule 1 expression and signaling in human, mouse, and rat leukocytes: evidence for replacement of the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked proteins in human leukocytes. J Immunol. 2002;168(10):5139–46.CrossRefPubMed
51.
Fiori V, Magnani M, Cianfriglia M. The expression and modulation of CEACAM1 and tumor cell transformation. Ann Ist Super Sanita. 2012;48(2):161–71.CrossRefPubMed
52.
Sappino AP, Buser R, Seguin Q, Fernet M, Lesne L, Gumy-Pause F, et al. The CEACAM1 tumor suppressor is an ATM and p53-regulated gene required for the induction of cellular senescence by DNA damage. Oncogenesis. 2012;1:e7.CrossRefPubMedPubMedCentral
53.
Tiernan JP, Perry SL, Verghese ET, West NP, Yeluri S, Jayne DG, et al. Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting. Br J Cancer. 2013;108(3):662–7.CrossRefPubMedPubMedCentral
54.
Thomas P, Forse RA, Bajenova O. Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver. Clin Exp Metastasis. 2011;28(8):923–32.CrossRefPubMed
55.
Zheng C, Feng J, Lu D, Wang P, Xing S, Coll JL, et al. A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity. PLoS One. 2011;6(6):e21146.CrossRefPubMedPubMedCentral
56.
Kim KS, Kim JT, Lee SJ, Kang MA, Choe IS, Kang YH, et al. Overexpression and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 6 in colorectal cancer. Clin Chim Acta. 2013;415:12–9.CrossRefPubMed
Metadata
Title
A549 cells adapted to high nitric oxide show reduced surface CEACAM expression and altered adhesion and migration properties
Authors
Madeeha Aqil
Kim M. Elseth
Ashok Arjunakani
Philip Nebres
Courtney P. Amegashie
Devang H. Thanki
Premal B. Desai
James A. Radosevich
Publication date
01-03-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2789-9

Other articles of this Issue 3/2015

Tumor Biology 3/2015 Go to the issue

Research Article

Positive expression of pro-opiomelanocortin (POMC) is a novel independent poor prognostic marker in surgically resected non-small cell lung cancer

Research Article

STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma

Review

Role of miR-155 in drug resistance of breast cancer

Research Article

NADPH oxidase 1-dependent ROS is crucial for TLR4 signaling to promote tumor metastasis of non-small cell lung cancer

Research Article

The polymorphism MMP1 −1607 (1G>2G) is associated with a significantly increased risk of cancers from a meta-analysis

Research Article

MiR-218 regulates cisplatin chemosensitivity in breast cancer by targeting BRCA1
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits