Imaging of HER2 may improve the outcome of external irradiation therapy for prostate cancer patients

Andersson,Jennie; Rosestedt,Maria; Orlova,Anna

doi:10.3892/ol.2014.2760

Imaging of HER2 may improve the outcome of external irradiation therapy for prostate cancer patients

Authors:
- Jennie Andersson
- Maria Rosestedt
- Anna Orlova
View Affiliations

Affiliations: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala 751 83, Sweden
Published online on: December 3, 2014 https://doi.org/10.3892/ol.2014.2760
Pages: 950-954

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Prostate cancer (PCa) is the most common type of cancer among males. Human epidermal growth factor receptor type 2 (HER2) expression in PCa has been reported by several studies and its involvement in the progression towards androgen‑independent PCa has been discussed. External irradiation is one of the existing therapies, which has been demonstrated to be efficient in combination with androgen deprivation therapy for the treatment of advanced PCa. However, 20‑40% of patients develop recurrent and more aggressive PCa within 10 years. The current study investigates the involvement of HER2 in survival and radioresistance in PCa cells and we hypothesized that, by monitoring HER2 expression, treatment may be personalized. The PCa cell lines, LNCap, PC3 and DU‑145, received a 6 Gy single dose of external irradiation. The number of PC3 cells was not affected by a single dose of radiation, whereas a 5‑fold decrease in cell number was detected in LNCap (P<0.00001) and DU‑145 (P<0.0001) cells. The HER2 expression in PC3 exhibited a significant increase post irradiation, however, the expression was stable in the remaining cell lines. The administration of trastuzumab post‑irradiation resulted in a 2‑fold decrease in the PC3 cell number, while the drug did not demonstrate additional effects in LNCap and DU‑145 cells, when compared with that of irradiation treatment alone. The results of the present study demonstrated that an increase in membranous HER2 expression in response to external irradiation may indicate cell radioresistance. Furthermore, imaging of HER2 expression prior to and following external irradiation may present a step towards personalized therapy in PCa.

View Figures

View References

1	Chen W, Mao K, Liu Z and Dinh-Xuan AT: The role of the RhoA/Rho kinase pathway in angiogenesis and its potential value in prostate cancer (Review). Oncol Lett. 8:1907–1911. 2014.PubMed/NCBI
2	Sieh W, Lichtensztajn DY, Nelson DO, et al: Treatment and mortality in men with localized prostate cancer: a population-based study in California. The Open Prost Cancer J. 6:1–9. 2013. View Article : Google Scholar
3	Widmark A, Klepp O, Solberg A, et al; Scandinavian Prostate Cancer Group Study 7; Swedish Association for Urological Oncology. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 373:301–308. 2009. View Article : Google Scholar
4	Pienta KJ and Bradley D: Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res. 12:1665–1671. 2006. View Article : Google Scholar : PubMed/NCBI
5	Harmenberg U, Hamdy FC, Widmark A, Lennernäs B and Nilsson S: Curative radiation therapy in prostate cancer. Acta Oncol. 50-1:98–103. 2011. View Article : Google Scholar
6	Kelloff GJ, Choyke P and Coffey DS: Prostate Cancer Imaging Working Group: Challenges in clinical prostate cancer: role of imaging. Am J Roentgenol. 192:1455–1470. 2009. View Article : Google Scholar
7	Petrylak DP, Tangen CM, Hussain MH, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 351:1513–1520. 2004. View Article : Google Scholar : PubMed/NCBI
8	Minner S, Jessen B, Stiedenroth L, et al: Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res. 16:1553–1560. 2010. View Article : Google Scholar : PubMed/NCBI
9	Yarden Y and Sliwkowski MX: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2:127–137. 2001. View Article : Google Scholar : PubMed/NCBI
10	Signoretti S, Montironi R, Manola J, et al: Her-2-neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst. 92:1918–1925. 2000. View Article : Google Scholar : PubMed/NCBI
11	Craft N, Shostak Y, Carey M and Sawyers CL: A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med. 5:280–285. 1999. View Article : Google Scholar : PubMed/NCBI
12	Culig Z, Hobisch A, Cronauer MV, et al: Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res. 54:5474–5478. 1994.PubMed/NCBI
13	Valerie K, Yacoub A, Hagan MP, Curiel DT, Fisher PB, Grant S and Dent P: Radiation induced cell signaling: inside-out and outside-in. Mol Cancer Ther. 6:789–801. 2007. View Article : Google Scholar : PubMed/NCBI
14	So A, Gleave M, Hurtado-Col A and Nelson C: Mechanisms of the development of androgen independence in prostate cancer. World J Urol. 23:1–9. 2005. View Article : Google Scholar : PubMed/NCBI
15	The US National Institutes of Health. Paclitaxel and radiation therapy with or without trastuzumab in treating patients who have undergone surgery for bladder cancer. NCT00238420. 2014, ClinicalTrials.govurisimpleClinicalTrials.gov.
16	The U.S National Institutes of Health. Evaluation of carboplatin/paclitaxel with and without trastuzumab (Herceptin) in uterine serous cancer. NCT01367002. 2014, ClinicalTrials.govurisimpleClinicalTrials.gov.
17	The U.S National Institutes of Health. Safety study of ²¹²Pb-TCMC-trastuzumab radio immunotherapy. NCT01384253. 2014, ClinicalTrials.govurisimpleClinicalTrials.gov.
18	Albanell J, Codony J, Rovira A, Mellado B and Gascón P: Mechanism of action of anti-HER2 monoclonal antibodies: scientific update on trastuzumab and 2C4. Adv Exp Med Biol. 532:253–268. 2003. View Article : Google Scholar : PubMed/NCBI
19	Malmberg J, Tolmachev V and Orlova A: Imaging agents for in vivo molecular profiling of disseminated prostate cancer: Cellular processing of [(111)In]-labeled CHX-A″DTPA-trastuzumab and anti-HER2 ABY-025 Affibody in prostate cancer cell lines. Exp Ther Med. 2:523–528. 2011.PubMed/NCBI
20	Ahlgren S, Orlova A, Wållberg H, et al: Targeting of HER2-expressing tumors using 111In-ABY-025, a second-generation affibody molecule with a fundamentally reengineered scaffold. J Nucl Med. 51:1131–1138. 2010. View Article : Google Scholar : PubMed/NCBI
21	Malmberg J, Tolmachev V and Orlova A: Imaging agents for in vivo molecular profiling of disseminated prostate cancer targeting EGFR receptors in prostate cancer: comparison of cellular processing of [111In]-labeled affibody molecule Z (EGFR:2377) and cetuximab. Int J Oncol. 41:1128–1138. 2011.
22	Baek KH, Hong ME, Jung YY, et al: Correlation of AR, EGFR, and HER2 Expression Levels in Prostate Cancer: Immunohistochemical Analysis and Chromogenic In Situ Hybridization. Cancer Res Treat. 44:50–56. 2012. View Article : Google Scholar : PubMed/NCBI
23	Carrion Salip D, Panosa C, Menendez JA, et al: Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands. Int J Oncol. 41:1128–1138. 2012.PubMed/NCBI
24	Malmberg J, Perols A, Varasteh Z, et al: Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with 111In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts. Eur J Nucl Med Mol Imaging. 39:481–492. 2012. View Article : Google Scholar : PubMed/NCBI
25	Wallberg H, Orlova A, Altai M, et al: Molecular design and optimization of 99mTc-labeled recombinant affibody molecules improves their biodistribution and imaging properties. J Nucl Med. 52:461–469. 2011. View Article : Google Scholar : PubMed/NCBI
26	Duru N, Fan M, Candas D, et al: HER2-associated radioresistance of breast cancer stem cells isolated from HER2-negative breast cancer cells. Clin Cancer Res. 18:6634–6647. 2012. View Article : Google Scholar : PubMed/NCBI
27	No M, Cho EJ and Kim IA: Targeting HER2 signaling pathway for radiosensitization: alternative strategy for therapeutic resistance. Cancer Biol Ther. 8:2351–2361. 2009. View Article : Google Scholar : PubMed/NCBI