Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jul 1;70(10):1066-73.
doi: 10.1002/pros.21140.

Effects of transplantation of adipose tissue-derived stem cells on prostate tumor

Guiting Lin  1 , Rong Yang, Lia Banie, Guifang Wang, Hongxiu Ning, Long-Cheng Li, Tom F Lue, Ching-Shwun Lin
Affiliations

Effects of transplantation of adipose tissue-derived stem cells on prostate tumor

Guiting Lin et al. Prostate. .

Abstract

Background: Obesity is a risk factor for prostate cancer development, but the underlying mechanism is unknown. The present study tested the hypothesis that stromal cells of the adipose tissue might be recruited by cancer cells to help tumor growth.

Methods: PC3 prostate cancer cells were transplanted into the subcutaneous space of the right flank of athymic mice. One week later, adipose tissue-derived stromal or stem cells (ADSC) or phosphate-buffered saline (PBS, as control) was transplanted similarly to the left flank. Tumor size was monitored for the next 34 days; afterwards, the mice were sacrificed and their tumors harvested for histological examination. The ability of PC3 cells to attract ADSC was tested by migration assay. The involvement of the CXCL12/CXCR4 axis was tested by migration assay in the presence of a specific inhibitor AMD3100.

Results: Throughout the entire course, the average size of PC3 tumors in ADSC-treated mice was larger than in PBS-treated mice. ADSC were identified inside the tumors of ADSC-treated mice; CXCR4 expression was also detected. Migration assay indicated the involvement of the CXCL12/CXCR4 axis in the migration of ADSC toward PC3 cells. Capillary density was twice as high in the tumors of ADSC-treated mice than in the tumors of PBS-treated mice. VEGF expression was similar but FGF2 expression was significantly higher in tumors of ADSC-treated mice than in the tumors of PBS-tread mice.

Conclusion: Prostate cancer cells recruited ADSC by the CXCL12/CXCR4 axis. ADSC helps tumor growth by increasing tumor vascularity, and which was mediated by FGF2.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Athymic mice (n = 20) were subcutaneously injected with PC3 prostate cancer cells into the right flank, followed 1 week later by the injection of ADSC (n = 10) or PBS (control, n = 10) into the left flank. Tumor growth was then monitored for 34 days. The average calculated tumor sizes are shown for the indicated time points.
Fig. 2
Fig. 2
A: After the last size measurement, tumors (a,c) from control and ADSC-treated mice, as well as the subcutaneous tissue of the ADSC injection site (b), were excised for histological examination. The tumors and subcutaneous tissues were stained with DAPI (blue) and EdU (red) for nuclear visualization and tracking of ADSC, respectively. a: Tumors from control mice had no ADSC. b: Subcutaneous tissue from ADSC-treated mice had many ADSC (arrows). c:Tumors from ADSC-treated mice also had ADSC (arrows). Original magnification is200×. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Fig. 3
Fig. 3
Tumors from control (upper panels) and ADSC-treated (lower panels) mice were stained with DAPI (blue), EdU (red), and CXCR4 (green). The insert (original magnification is 1,000×) shown at the upper right corner of each graph (original magnification is 200×) is the enlargement of the boxed area near the center of the graph. Arrowhead points to a representative nucleus, which was co-stained with EdU and CXCR4. Arrows point to cytoplasmic or membrane expression CXCR4. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Fig. 4
Fig. 4
A: The conditioned medium of PC3 cells or human cavernous smooth muscle cells (HCSMC) was assessed for ability to attract ADSC. The number of attracted ADSC is shown in the Y-axis. * indicates P <0.05 when compared to HCSMC control. B: The conditioned medium of PC3 cells was assessed for ability to attract ADSC, which was treated with AMD3100 at the indicated concentrations for1hr prior. * indicates P <0.05 when compared to 0 μM control. C:The conditioned medium ofPC3 cells was assessed for ability to attract HCSMC, which was treated with AMD3100 at the indicated concentrations for1hrprior.
Fig. 5
Fig. 5
Tumors from control and ADSC-treated mice were stained with DAPI (blue) and CD31 (green). The number of capillaries per field was determined by counting each contiguous green stain as one capillary (arrows). The average capillary numbers per field in all 10 tumors of control mice and all 10 tumors of ADSC-treated mice are shown in the bar chart. * indicates P <0.05 when compared to control. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Fig. 6
Fig. 6
Tumors from ADSC-treated mice were stained with DAPI (blue), EdU (red), and VEGF (green). VEGF expression level was determined by counting the pixel number of all green stains per field at 200× magnification. The average pixel numbers per field in all 10 tumors of control mice and all10 tumors of ADSC-treated mice are shown in the bar chart. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Fig. 7
Fig. 7
Tumors from ADSC-treated mice were stained with DAPI (blue), EdU (red), and FGF2 (green). A representative EdU+ cell, which was infrequently seen in strongly FGF2+ areas, is shown in the insert (original magnification is 1,000×). The average numbers of FGF2-expressing cells per field at 200× in all10 tumors of control mice and all 10 tumors of ADSC-treated mice are shown in the bar chart. * indicates P <0.05 when compared to control. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV, Thun MJ, Calle EE. Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev. 2007;16(1):63–69. - PubMed
    1. Park JH, Cho BL, Kwon HT, Lee CM, Han HJ. Effect of body mass index and waist circumference on prostate specific antigen and prostate volume in a generally healthy Korean population. J Urol. 2009;182(1):106–110. discussion 110–101. - PubMed
    1. Freedland SJ, Banez LL, Sun LL, Fitzsimons NJ, Moul JW. Obese men have higher-grade and larger tumors: An analysis of the duke prostate center database. Prostate Cancer Prostatic Dis. 2009;12(3):259–263. - PubMed
    1. Muehlberg FL, Song YH, Krohn A, Pinilla SP, Droll LH, Leng X, Seidensticker M, Ricke J, Altman AM, Devarajan E, Liu W, Arlinghaus RB, Alt EU. Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis. 2009;30(4):589–597. - PubMed
    1. Walter M, Liang S, Ghosh S, Hornsby PJ, Li R. Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene. 2009;28(30):2745–2755. - PMC - PubMed

Publication types

MeSH terms