CD117 Expression in Fibroblasts-Like Stromal Cells Indicates Unfavorable Clinical Outcomes in Ovarian Carcinoma Patients

被引:25
作者
Huang, Ruixia [1 ,2 ]
Wu, Dan [3 ]
Yuan, Yuan [4 ]
Li, Xiaoran [1 ,2 ]
Holm, Ruth [1 ]
Trope, Claes G. [5 ,6 ]
Nesland, Jahn M. [1 ,2 ]
Suo, Zhenhe [1 ,2 ]
机构
[1] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway
[2] Univ Oslo, Fac Med, Inst Clin Med, Dept Pathol, Oslo, Norway
[3] Shanghai Jiao Tong Univ, Int Peace Matern & Child Hlth Hosp, Med Coll Shanghai, Dept Gynecol, Shanghai 200030, Peoples R China
[4] Capital Med Univ, Dept Pathol, Beijing, Peoples R China
[5] Univ Oslo, Fac Med, Inst Clin Med, Dept Gynecol, Oslo, Norway
[6] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Gynecol, Oslo, Norway
关键词
EPITHELIAL-MESENCHYMAL TRANSITIONS; ACTIVATION PROTEIN; STEM-CELLS; C-KIT; CANCER; TUMORS; CHALLENGES; MARKERS; BETA;
D O I
10.1371/journal.pone.0112209
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The stem cell factor (SCF) receptor CD117 (c-kit), is widely used for identification of hematopoietic stem cells and cancer stem cells. Moreover, CD117 expression in carcinoma cells indicates a poor prognosis in a variety of cancers. However the potential expression in tumor microenvironment and the biological and clinical impact are currently not reported. The expression of CD117 was immunohistochemically evaluated in a serial of 242 epithelial ovarian cancer (EOC) cases. Thirty-eight out of 242 cases were CD117 positive in fibroblast-like stromal cells and 22 cases were positive in EOC cells. Four cases were both positive in fibroblast-like stromal cells and EOC cells for CD117. CD117 expression in fibroblast-like stromal cells in ovarian carcinoma was closely linked to advanced FIGO stage, poor differentiation grade and histological subtype (p<0.05), and it was significantly associated with poor overall survival (OS) and progression free survival (PFS) (Kaplan-Meier analysis; p<0.05, log-rank test). CD117 expression in ovarian carcinoma cells was not associated with these clinicopathological variables. The CD117 positive fibroblast-like stromal cells were all positive for mesenchymal stem/stromal cell (MSC) marker CD73 but negative for fibroblast markers fibroblast activation protein (FAP) and alpha smooth muscle actin (alpha-SMA), indicating that the CD117+/CD73+ fibroblast-like stromal cells are a subtype of mesenchymal stem cells in tumor stroma, although further characterization of these cells are needed. It is concluded herewith that the presence of CD117+/CD73+ fibroblast-like stromal cells in ovarian carcinoma is an unfavorable clinical outcome indication.
引用
收藏
页数:9
相关论文
共 58 条
[1]   CD117 and Stro-1 Identify Osteosarcoma Tumor-Initiating Cells Associated with Metastasis and Drug Resistance [J].
Adhikari, Amit S. ;
Agarwal, Neeraj ;
Wood, Byron M. ;
Porretta, Constance ;
Ruiz, Bernardo ;
Pochampally, Radhika R. ;
Iwakuma, Tomoo .
CANCER RESEARCH, 2010, 70 (11) :4602-4612
[2]   The tumour microenvironment as a target for chemoprevention [J].
Albini, Adriana ;
Sporn, Michael B. .
NATURE REVIEWS CANCER, 2007, 7 (02) :139-147
[3]   Anti-CD73 therapy impairs tumor angiogenesis [J].
Allard, Bertrand ;
Turcotte, Martin ;
Spring, Kathleen ;
Pommey, Sandra ;
Royal, Isabelle ;
Stagg, John .
INTERNATIONAL JOURNAL OF CANCER, 2014, 134 (06) :1466-1473
[4]   CD73-Generated Adenosine: Orchestrating the Tumor-Stroma Interplay to Promote Cancer Growth [J].
Allard, Bertrand ;
Turcotte, Martin ;
Stagg, John .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2012,
[5]  
Anker PSI, 2003, HAEMATOLOGICA, V88, P845
[6]   Fibroblast activation protein α identifies mesenchymal stromal cells from human bone marrow [J].
Bae, Sohyun ;
Park, Chae Woon ;
Son, Hye Kyung ;
Ju, Hye Kyung ;
Paik, Donggi ;
Jeon, Choon-Ju ;
Koh, Gou Young ;
Kim, Jaeseob ;
Kim, Hoeon .
BRITISH JOURNAL OF HAEMATOLOGY, 2008, 142 (05) :827-830
[7]   Markers for Characterization of Bone Marrow Multipotential Stromal Cells [J].
Boxall, Sally A. ;
Jones, Elena .
STEM CELLS INTERNATIONAL, 2012, 2012
[8]   Rationale Behind Targeting Fibroblast Activation Protein-Expressing Carcinoma-Associated Fibroblasts as a Novel Chemotherapeutic Strategy [J].
Brennen, W. Nathaniel ;
Isaacs, John T. ;
Denmeade, Samuel R. .
MOLECULAR CANCER THERAPEUTICS, 2012, 11 (02) :257-266
[9]   Diversity, topographic differentiation, and positional memory in human fibroblasts [J].
Chang, HY ;
Chi, JT ;
Dudoit, S ;
Bondre, C ;
van de Rijn, M ;
Botstein, D ;
Brown, PO .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12877-12882
[10]   Natural killer cells acquire CD73 expression upon exposure to mesenchymal stem cells [J].
Chatterjee, Debanjana ;
Tufa, Dejene Milkessa ;
Baehre, Heike ;
Hass, Ralf ;
Schmidt, Reinhold Ernst ;
Jacobs, Roland .
BLOOD, 2014, 123 (04) :594-595