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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

mRFP-labeled SCLC cell number after co-culturing with CAFs(A) Total viable NCI-H82 cell numbers after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (B) Total viable NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (C) Total viable PC9 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN.
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Figure 2: mRFP-labeled SCLC cell number after co-culturing with CAFs(A) Total viable NCI-H82 cell numbers after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (B) Total viable NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (C) Total viable PC9 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN.

Mentions: We co-cultured mRFP-labeled SCLC cell lines (NCI-H82 and NCI-H69) with Venus-labeled CAFs expressing WT-PDPN (CAFs-PDPN) or CAFs-Control (CAFs-Ctrl); after 4 days, we then counted the number of viable NCI-H82 cells. When mRFP-labeled NCI-H82 was cultured alone, the number of 7-AAD-positive cells significantly decreased and the viable cell number increased to 127.6% of cancer cell co-cultured with CAFs-Ctrl (Supplementary Figure 2). Co-culture with CAFs-PDPN suppressed the viable NCI-H82 cancer cell number to 84.5% of the number of cancer cells after co-culturing with CAFs-Ctrl (P < 0.01) (Figure 2A). CAFs-PDPN did not affect the number of dead cancer cells (7-AAD-positive cancer cells, P = 0.59). We also used another SCLC cell line, NCI-H69, and confirmed similar results. Co-culture with CAFs-PDPN decreased the viable NCI-H69 cell number to 79.5% of the number of cancer cells after co-culturing with CAFs-Ctrl (P < 0.01) (Figure 2B).


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)

mRFP-labeled SCLC cell number after co-culturing with CAFs(A) Total viable NCI-H82 cell numbers after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (B) Total viable NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (C) Total viable PC9 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: mRFP-labeled SCLC cell number after co-culturing with CAFs(A) Total viable NCI-H82 cell numbers after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (B) Total viable NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (left). Total 7-AAD-positive NCI-H69 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN (right). (C) Total viable PC9 cell number after co-culturing with CAFs-Ctrl or CAFs-PDPN.
Mentions: We co-cultured mRFP-labeled SCLC cell lines (NCI-H82 and NCI-H69) with Venus-labeled CAFs expressing WT-PDPN (CAFs-PDPN) or CAFs-Control (CAFs-Ctrl); after 4 days, we then counted the number of viable NCI-H82 cells. When mRFP-labeled NCI-H82 was cultured alone, the number of 7-AAD-positive cells significantly decreased and the viable cell number increased to 127.6% of cancer cell co-cultured with CAFs-Ctrl (Supplementary Figure 2). Co-culture with CAFs-PDPN suppressed the viable NCI-H82 cancer cell number to 84.5% of the number of cancer cells after co-culturing with CAFs-Ctrl (P < 0.01) (Figure 2A). CAFs-PDPN did not affect the number of dead cancer cells (7-AAD-positive cancer cells, P = 0.59). We also used another SCLC cell line, NCI-H69, and confirmed similar results. Co-culture with CAFs-PDPN decreased the viable NCI-H69 cell number to 79.5% of the number of cancer cells after co-culturing with CAFs-Ctrl (P < 0.01) (Figure 2B).

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