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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 inducing shRNA PDPN(A) Flow cytometry analysis of PDPN expression in CAFs-Ctrl, CAFs-shPDPN1, and CAFs-shPDPN3. (B) Total viable NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (right).
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Figure 3: mRFP-labeled SCLC cell number after co-culturing with CAFs inducing shRNA PDPN(A) Flow cytometry analysis of PDPN expression in CAFs-Ctrl, CAFs-shPDPN1, and CAFs-shPDPN3. (B) Total viable NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (right).

Mentions: We prepared two different PDPN knockdown CAFs (CAFs-shPDPN1 and CAFs-shPDPN3) [25] (Figure 3A). Co-culture with CAFs-shPDPN1 and CAFs-shPDPN3 significantly increased the number of viable NCI-H82 cancer cells to 129.2% and 125.6%, respectively, of the number of cancer cells after co-culturing with CAFs-Ctrl (P < 0.01 and P < 0.01). CAFs-shPDPN1 increased the number of dead cancer cells (P = 0.04), but co-culturing with CAFs-shPDPN3 did not have any effect (P = 0.25) (Figure 3B).


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 inducing shRNA PDPN(A) Flow cytometry analysis of PDPN expression in CAFs-Ctrl, CAFs-shPDPN1, and CAFs-shPDPN3. (B) Total viable NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (right).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: mRFP-labeled SCLC cell number after co-culturing with CAFs inducing shRNA PDPN(A) Flow cytometry analysis of PDPN expression in CAFs-Ctrl, CAFs-shPDPN1, and CAFs-shPDPN3. (B) Total viable NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (left). Total 7-AAD-positive NCI-H82 cell number after co-culturing with CAFs-Ctrl, CAFs-shPDPN1, or CAFs-shPDPN3 (right).
Mentions: We prepared two different PDPN knockdown CAFs (CAFs-shPDPN1 and CAFs-shPDPN3) [25] (Figure 3A). Co-culture with CAFs-shPDPN1 and CAFs-shPDPN3 significantly increased the number of viable NCI-H82 cancer cells to 129.2% and 125.6%, respectively, of the number of cancer cells after co-culturing with CAFs-Ctrl (P < 0.01 and P < 0.01). CAFs-shPDPN1 increased the number of dead cancer cells (P = 0.04), but co-culturing with CAFs-shPDPN3 did not have any effect (P = 0.25) (Figure 3B).

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