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Matched pairs of human prostate stromal cells display differential tropic effects on LNCaP prostate cancer cells.

Sun X, He H, Xie Z, Qian W, Zhau HE, Chung LW, Marshall FF, Wang R - In Vitro Cell. Dev. Biol. Anim. (2010)

Bottom Line: However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival.Growth and survival of these clones are not affected by androgens.The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability.

View Article: PubMed Central - PubMed

Affiliation: Molecular Urology and Therapeutics, Department of Urology and Winship Cancer Institute, Emory University School of Medicine, 1365B Clifton Road, NE, Suite B5103, Atlanta, GA 30322, USA.

ABSTRACT
Prostate stromal cells may play binary roles in the process of prostate cancer development. As the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal clones. In this report, we describe the morphologic and behavioral characteristics of these cells and their effect on LNCaP prostate cancer cells in co-culture. Unlike LNCaP prostate cancer cells, the isolated prostate stromal clones are large fibroblast-like cells with a slow proliferation rate. Growth and survival of these clones are not affected by androgens. The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability. In co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. This work thus established a panel of valuable human prostate stromal cell lines, which could be used in co-culture to study the interaction between prostate cancer and prostate stromal cells.

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Stromal cells render LNCaP cells resistant to starvation-induced death. Representative results from co-culture with the HPS-15 stromal clone are shown. A PSA production in the co-cultures (LNCaP+HPS-15 and RL-1+HPS-15) was detected throughout the serum starvation. In comparison, PSA was lost when cancer cells alone (LNCaP and RL-1) were subjected to starvation. PSA is not expressed in HPS-15 stromal cells (HPS-15). Data represent the mean of triplicate assays. Standard deviation for each data is less than 5% of the mean and is not shown. B When RL-1 cells were cultured alone, the loss of PSA production was due to cell death under serum starvation. Shown are cultures of RL-1 alone at the beginning (Day 1) and at Day 35 of serum starvation. All RL-1 cells died after 35 d of serum starvation. For fluorescence photography, a phase contrast microphotograph (upper panel) and red fluorescence image (lower panel) of the same field are shown. C Co-cultures of RL-1 with HPS-15 at the beginning (Day 1) and end (Day 60) of serum starvation. Representative surviving RL-1 cells (arrows) are shown among stromal cells. D After a 60-d serum starvation, surviving RL-1 cells from the co-culture formed colonies (arrows) among stromal cell colonies upon replating in normal culture medium for 14 d. Two representative results are shown.
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Fig4: Stromal cells render LNCaP cells resistant to starvation-induced death. Representative results from co-culture with the HPS-15 stromal clone are shown. A PSA production in the co-cultures (LNCaP+HPS-15 and RL-1+HPS-15) was detected throughout the serum starvation. In comparison, PSA was lost when cancer cells alone (LNCaP and RL-1) were subjected to starvation. PSA is not expressed in HPS-15 stromal cells (HPS-15). Data represent the mean of triplicate assays. Standard deviation for each data is less than 5% of the mean and is not shown. B When RL-1 cells were cultured alone, the loss of PSA production was due to cell death under serum starvation. Shown are cultures of RL-1 alone at the beginning (Day 1) and at Day 35 of serum starvation. All RL-1 cells died after 35 d of serum starvation. For fluorescence photography, a phase contrast microphotograph (upper panel) and red fluorescence image (lower panel) of the same field are shown. C Co-cultures of RL-1 with HPS-15 at the beginning (Day 1) and end (Day 60) of serum starvation. Representative surviving RL-1 cells (arrows) are shown among stromal cells. D After a 60-d serum starvation, surviving RL-1 cells from the co-culture formed colonies (arrows) among stromal cell colonies upon replating in normal culture medium for 14 d. Two representative results are shown.

Mentions: Cancer-associated prostate stromal cells rescue LNCaP prostate cancer cells from starvation-induced death. Stromal cells of the tumor microenvironment may promote cancer cell survival through mechanisms of cancer–stromal interaction (Sung and Chung 2002; Kogan-Sakin et al. 2009). Since the prostate stromal clones were insensitive to androgen and were highly resistant to serum starvation (Figs. 2 and 3), we assessed whether the stromal clones could promote survival of prostate cancer cells under similar conditions. The study was conducted by co-culturing the stromal cells with LNCaP prostate cancer cells. To prepare for co-culture, stromal cells were first grown to form a confluent monolayer completely covering the plastic surface of the culture ware. After removal of the culture medium, LNCaP prostate cancer cells were overlaid onto the monolayer in low density, so the co-culture was comprised of equal numbers of stromal and cancer cells.Cells in the co-culture were treated with serum starvation for 60 d. During the treatment, most of the LNCaP cells died gradually, as seen by microscopic inspection and detected by markedly reduced PSA in the culture medium (Fig. 4A). The low PSA level, however, was sustained to the end of the experiment at 60 d. Since none of the prostate stromal clones expressed detectable levels of PSA by ELISA (Fig. 4A and data not shown), these results suggested that some LNCaP cells had survived the starvation.Figure 4.


Matched pairs of human prostate stromal cells display differential tropic effects on LNCaP prostate cancer cells.

Sun X, He H, Xie Z, Qian W, Zhau HE, Chung LW, Marshall FF, Wang R - In Vitro Cell. Dev. Biol. Anim. (2010)

Stromal cells render LNCaP cells resistant to starvation-induced death. Representative results from co-culture with the HPS-15 stromal clone are shown. A PSA production in the co-cultures (LNCaP+HPS-15 and RL-1+HPS-15) was detected throughout the serum starvation. In comparison, PSA was lost when cancer cells alone (LNCaP and RL-1) were subjected to starvation. PSA is not expressed in HPS-15 stromal cells (HPS-15). Data represent the mean of triplicate assays. Standard deviation for each data is less than 5% of the mean and is not shown. B When RL-1 cells were cultured alone, the loss of PSA production was due to cell death under serum starvation. Shown are cultures of RL-1 alone at the beginning (Day 1) and at Day 35 of serum starvation. All RL-1 cells died after 35 d of serum starvation. For fluorescence photography, a phase contrast microphotograph (upper panel) and red fluorescence image (lower panel) of the same field are shown. C Co-cultures of RL-1 with HPS-15 at the beginning (Day 1) and end (Day 60) of serum starvation. Representative surviving RL-1 cells (arrows) are shown among stromal cells. D After a 60-d serum starvation, surviving RL-1 cells from the co-culture formed colonies (arrows) among stromal cell colonies upon replating in normal culture medium for 14 d. Two representative results are shown.
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Fig4: Stromal cells render LNCaP cells resistant to starvation-induced death. Representative results from co-culture with the HPS-15 stromal clone are shown. A PSA production in the co-cultures (LNCaP+HPS-15 and RL-1+HPS-15) was detected throughout the serum starvation. In comparison, PSA was lost when cancer cells alone (LNCaP and RL-1) were subjected to starvation. PSA is not expressed in HPS-15 stromal cells (HPS-15). Data represent the mean of triplicate assays. Standard deviation for each data is less than 5% of the mean and is not shown. B When RL-1 cells were cultured alone, the loss of PSA production was due to cell death under serum starvation. Shown are cultures of RL-1 alone at the beginning (Day 1) and at Day 35 of serum starvation. All RL-1 cells died after 35 d of serum starvation. For fluorescence photography, a phase contrast microphotograph (upper panel) and red fluorescence image (lower panel) of the same field are shown. C Co-cultures of RL-1 with HPS-15 at the beginning (Day 1) and end (Day 60) of serum starvation. Representative surviving RL-1 cells (arrows) are shown among stromal cells. D After a 60-d serum starvation, surviving RL-1 cells from the co-culture formed colonies (arrows) among stromal cell colonies upon replating in normal culture medium for 14 d. Two representative results are shown.
Mentions: Cancer-associated prostate stromal cells rescue LNCaP prostate cancer cells from starvation-induced death. Stromal cells of the tumor microenvironment may promote cancer cell survival through mechanisms of cancer–stromal interaction (Sung and Chung 2002; Kogan-Sakin et al. 2009). Since the prostate stromal clones were insensitive to androgen and were highly resistant to serum starvation (Figs. 2 and 3), we assessed whether the stromal clones could promote survival of prostate cancer cells under similar conditions. The study was conducted by co-culturing the stromal cells with LNCaP prostate cancer cells. To prepare for co-culture, stromal cells were first grown to form a confluent monolayer completely covering the plastic surface of the culture ware. After removal of the culture medium, LNCaP prostate cancer cells were overlaid onto the monolayer in low density, so the co-culture was comprised of equal numbers of stromal and cancer cells.Cells in the co-culture were treated with serum starvation for 60 d. During the treatment, most of the LNCaP cells died gradually, as seen by microscopic inspection and detected by markedly reduced PSA in the culture medium (Fig. 4A). The low PSA level, however, was sustained to the end of the experiment at 60 d. Since none of the prostate stromal clones expressed detectable levels of PSA by ELISA (Fig. 4A and data not shown), these results suggested that some LNCaP cells had survived the starvation.Figure 4.

Bottom Line: However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival.Growth and survival of these clones are not affected by androgens.The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability.

View Article: PubMed Central - PubMed

Affiliation: Molecular Urology and Therapeutics, Department of Urology and Winship Cancer Institute, Emory University School of Medicine, 1365B Clifton Road, NE, Suite B5103, Atlanta, GA 30322, USA.

ABSTRACT
Prostate stromal cells may play binary roles in the process of prostate cancer development. As the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal clones. In this report, we describe the morphologic and behavioral characteristics of these cells and their effect on LNCaP prostate cancer cells in co-culture. Unlike LNCaP prostate cancer cells, the isolated prostate stromal clones are large fibroblast-like cells with a slow proliferation rate. Growth and survival of these clones are not affected by androgens. The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability. In co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. This work thus established a panel of valuable human prostate stromal cell lines, which could be used in co-culture to study the interaction between prostate cancer and prostate stromal cells.

Show MeSH
Related in: MedlinePlus