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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

An aggressive RhoC phenotype is associated with relapse after external beam radiation therapy of a prostate cancer xenograft model.

Sub-category:
Tissue-Based Biomarkers

Category:
Developmental Therapeutics and Tumor Biology (Nonimmuno)

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e14748

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e14748)

Author(s): Oskar Vilhelmsson Timmermand, Sven-Erik Strand, Crister Ceberg, Jens Adam Ceder; Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden; Department of Clinical Sciences Lund, Division of Medical Radiation Physics, Lund University, Lund, Sweden

Abstract Disclosures

Abstract:

Background: Relapsed treatment resistant prostate cancer remains the second most common cause of male mortality in the western world. New therapies for therapy resistant prostate cancer depend on defining tumor cell sub-populations capable of surviving, reinitiating, and sustaining net growth of the cancer. In this study we focused on RhoC expression in a prostate cancer model after external beam radiation therapy (EBRT). RhoC has earlier been implicated in metastatic processes in most solid tumors. Methods: In mice, established s.c. LNCaP xenografts (n = 12) were irradiated, the beam collimated with lead to restrict it to the xenograft, with X-rays (200 kV, 1 Gymin-1, Gulmay Medical) for an absorbed dose of 15 Gy. Tumor tissue was collected after seven days or after 3-4 weeks when recurrent growth was seen. RhoC, AR, CD166 and Ki67 immunohistochemistry in tumor sections was visualized by using DAB or Peroxidase Green and nuclear red or haematoxylin blue as counter stain. Sections stained for RhoC and Ki67 were quantified with the Halo software (v2.3.2089.34) using the Indica Labs – cytonuclear v1.6 algorithm. The intensity of the RhoC staining was also quantified in a separate set of sections only stained for RhoC. Results: The RhoC staining intensity was significantly higher in relapsed xenografts (P = 0.003). Also, a significant difference in percentage of RhoC expressing cells in the two populations (P = 0.045) with 40.6 ± 5.8% (mean ± SEM) in relapsed tumors as compared to 15.0 ± 8.1% after 7d. The percentage of cells expressing Ki67 was not significantly different (P = 0.477). However, the percentage of double positive cells (Ki67, RhoC) was significantly higher in treated relapsed xenografts (P = 0.042). Further, a subpopulation of RhoC-positive cells were positive for AR and the stem cell marker CD166. Conclusions: Here we show that a subpopulation of proliferating RhoC-positive cells are more prevalent in relapsing PCa xenografts after EBRT, suggesting an aggressive phenotype that is associated with both proliferation and invasiveness. Another subpopulation of RhoC cells was found to express the prostate stem cell marker CD166, suggesting that pathways and properties involved in cellular self-renewal and invasiveness may be responsible for survival and recurrent growth in relapsed prostate tumors.

 
Other Abstracts in this Sub-Category:

 

1. Cytoplasmic cyclin E independently predicts recurrence in older patients with primary breast cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3128 First Author: Simon Johnston
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Tissue-Based Biomarkers

 

2. Clinicopathologic characteristics of NRG1 fusion-positive cancers: A single-institution study.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3129 First Author: Alison M. Schram
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Tissue-Based Biomarkers

 

3. Molecular differences between lymph nodes (LNs) and distant metastases (mets) in colorectal cancer (CRC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 3130 First Author: Alberto Puccini
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Tissue-Based Biomarkers

 

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