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Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth.

Takahashi A, Ishii G, Neri S, Yoshida T, Hashimoto H, Suzuki S, Umemura S, Matsumoto S, Yoh K, Niho S, Goto K, Ohmatsu H, Nagai K, Gemma A, Ohe Y, Ochiai A - Oncotarget (2015)

Bottom Line: Cancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) are a favorable prognosticator in surgically resected small cell lung cancer (SCLC).Suppression of PDPN expression by shRNA in CAFs resulted in increased numbers of SCLC cells.In surgically resected human SCLC specimens, the frequency of Geminin-positive cancer cells was significantly higher in the cases with PDPN-positive CAFs than in the cases with PDPN-negative CAFs.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.

ABSTRACT
Cancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) are a favorable prognosticator in surgically resected small cell lung cancer (SCLC). Here we explore whether CAFs expressing PDPN influence proliferation of SCLC cells. Compared with control group (SCLC cells co-cultured with CAFs-Ctrl), numbers of SCLC cells co-cultured with CAFs overexpressing PDPN were decreased. Suppression of PDPN expression by shRNA in CAFs resulted in increased numbers of SCLC cells. In surgically resected human SCLC specimens, the frequency of Geminin-positive cancer cells was significantly higher in the cases with PDPN-positive CAFs than in the cases with PDPN-negative CAFs. Thus CAFs expressing PDPN inhibit growth of SCLC cells, suggesting that CAFs expressing PDPN represent a tumor inhibitory stromal cell component in SCLC.

No MeSH data available.


Related in: MedlinePlus

Co-culture model of SCLC cell lines and cancer-associated fibroblasts (CAFs)(A) Scheme of experimental procedure. (B) Phase contrast image (left upper), mRFP-labeled cancer cells (right upper), Venus-labeled CAFs (left lower), and 7AAD-positive cancer cells (right lower) as viewed using an optical microscope.
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Figure 1: Co-culture model of SCLC cell lines and cancer-associated fibroblasts (CAFs)(A) Scheme of experimental procedure. (B) Phase contrast image (left upper), mRFP-labeled cancer cells (right upper), Venus-labeled CAFs (left lower), and 7AAD-positive cancer cells (right lower) as viewed using an optical microscope.

Mentions: The mRFP-labeled cancer cells (2 × 105 cells) in RPMI1640 and the Venus-labeled CAFs (2 × 105 cells) in MEM alpha were equally mixed and plated onto a 60-mm dish (Figure 1A). On day 4, the number of mRFP-labeled cancer cells and the number of 7AAD (Beckman Coulter, CA)-positive cancer cells were measured using hemocytometers with an inverted-type fluorescence microscope (BZ-9000; KEYENCE, Japan) (Figure 1B). We defined dead tumor cells as both 7AAD-positive and mRFP-positive cells. On the hand, viable tumor cells were defined as mRFP-positive and 7AAD-negative cells. We calculated the percentage of cancer cells in each experiment using a denominator that represented the average value of the control group.


Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth.

Takahashi A, Ishii G, Neri S, Yoshida T, Hashimoto H, Suzuki S, Umemura S, Matsumoto S, Yoh K, Niho S, Goto K, Ohmatsu H, Nagai K, Gemma A, Ohe Y, Ochiai A - Oncotarget (2015)

Co-culture model of SCLC cell lines and cancer-associated fibroblasts (CAFs)(A) Scheme of experimental procedure. (B) Phase contrast image (left upper), mRFP-labeled cancer cells (right upper), Venus-labeled CAFs (left lower), and 7AAD-positive cancer cells (right lower) as viewed using an optical microscope.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496236&req=5

Figure 1: Co-culture model of SCLC cell lines and cancer-associated fibroblasts (CAFs)(A) Scheme of experimental procedure. (B) Phase contrast image (left upper), mRFP-labeled cancer cells (right upper), Venus-labeled CAFs (left lower), and 7AAD-positive cancer cells (right lower) as viewed using an optical microscope.
Mentions: The mRFP-labeled cancer cells (2 × 105 cells) in RPMI1640 and the Venus-labeled CAFs (2 × 105 cells) in MEM alpha were equally mixed and plated onto a 60-mm dish (Figure 1A). On day 4, the number of mRFP-labeled cancer cells and the number of 7AAD (Beckman Coulter, CA)-positive cancer cells were measured using hemocytometers with an inverted-type fluorescence microscope (BZ-9000; KEYENCE, Japan) (Figure 1B). We defined dead tumor cells as both 7AAD-positive and mRFP-positive cells. On the hand, viable tumor cells were defined as mRFP-positive and 7AAD-negative cells. We calculated the percentage of cancer cells in each experiment using a denominator that represented the average value of the control group.

Bottom Line: Cancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) are a favorable prognosticator in surgically resected small cell lung cancer (SCLC).Suppression of PDPN expression by shRNA in CAFs resulted in increased numbers of SCLC cells.In surgically resected human SCLC specimens, the frequency of Geminin-positive cancer cells was significantly higher in the cases with PDPN-positive CAFs than in the cases with PDPN-negative CAFs.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.

ABSTRACT
Cancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) are a favorable prognosticator in surgically resected small cell lung cancer (SCLC). Here we explore whether CAFs expressing PDPN influence proliferation of SCLC cells. Compared with control group (SCLC cells co-cultured with CAFs-Ctrl), numbers of SCLC cells co-cultured with CAFs overexpressing PDPN were decreased. Suppression of PDPN expression by shRNA in CAFs resulted in increased numbers of SCLC cells. In surgically resected human SCLC specimens, the frequency of Geminin-positive cancer cells was significantly higher in the cases with PDPN-positive CAFs than in the cases with PDPN-negative CAFs. Thus CAFs expressing PDPN inhibit growth of SCLC cells, suggesting that CAFs expressing PDPN represent a tumor inhibitory stromal cell component in SCLC.

No MeSH data available.


Related in: MedlinePlus