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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

Frequency of Geminin-positive SCLC cells in surgical specimens with CAFs-PDPN and those without CAFs-PDPN(A) Immunohistochemical staining for PDPN (upper) and Geminin (lower). The left figure shows a case without CAFs-PDPN, while the right shows a case with CAFs-PDPN. (B) Proportion of Geminin-positive SCLC cells. (C) Proportion of Geminin-positive adenocarcinoma cells.
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Figure 5: Frequency of Geminin-positive SCLC cells in surgical specimens with CAFs-PDPN and those without CAFs-PDPN(A) Immunohistochemical staining for PDPN (upper) and Geminin (lower). The left figure shows a case without CAFs-PDPN, while the right shows a case with CAFs-PDPN. (B) Proportion of Geminin-positive SCLC cells. (C) Proportion of Geminin-positive adenocarcinoma cells.

Mentions: To verify the in vitro results, we examined the frequency of Geminin-positive cancer cells in cases with PDPN-positive CAFs and those with PDPN-negative CAFs among surgically resected SCLC specimens (Table 1). Fourteen of the 36 specimens (38.9%) were PDPN-positive CAFs cases. Among the cases with PDPN-positive CAFs, 19.0% ± 1.7% of the SCLC cells showed a positive reaction for Geminin. However, 28.8% ± 1.6% of the SCLC cells showed a positive reaction for Geminin among the cases with PDPN-negative CAFs (P < 0.01) (Figure 5A and 5B). We also examined the frequency of Geminin-positive cancer cells of invasive lung adenocarcinoma with a tumor size of 2–3 cm in diameter (Cases with PDPN-positive CAFs vs Cases with PDPN-negative CAFs, n = 20, each). Adenocarcinoma cells in the cases with PDPN-positive cases showed significant higher positive ratio for Geminin than in the cases with PDPN-negative CAFs (9.2% vs 2.5%, p < 0.01) (Figure 5C).


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)

Frequency of Geminin-positive SCLC cells in surgical specimens with CAFs-PDPN and those without CAFs-PDPN(A) Immunohistochemical staining for PDPN (upper) and Geminin (lower). The left figure shows a case without CAFs-PDPN, while the right shows a case with CAFs-PDPN. (B) Proportion of Geminin-positive SCLC cells. (C) Proportion of Geminin-positive adenocarcinoma cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Frequency of Geminin-positive SCLC cells in surgical specimens with CAFs-PDPN and those without CAFs-PDPN(A) Immunohistochemical staining for PDPN (upper) and Geminin (lower). The left figure shows a case without CAFs-PDPN, while the right shows a case with CAFs-PDPN. (B) Proportion of Geminin-positive SCLC cells. (C) Proportion of Geminin-positive adenocarcinoma cells.
Mentions: To verify the in vitro results, we examined the frequency of Geminin-positive cancer cells in cases with PDPN-positive CAFs and those with PDPN-negative CAFs among surgically resected SCLC specimens (Table 1). Fourteen of the 36 specimens (38.9%) were PDPN-positive CAFs cases. Among the cases with PDPN-positive CAFs, 19.0% ± 1.7% of the SCLC cells showed a positive reaction for Geminin. However, 28.8% ± 1.6% of the SCLC cells showed a positive reaction for Geminin among the cases with PDPN-negative CAFs (P < 0.01) (Figure 5A and 5B). We also examined the frequency of Geminin-positive cancer cells of invasive lung adenocarcinoma with a tumor size of 2–3 cm in diameter (Cases with PDPN-positive CAFs vs Cases with PDPN-negative CAFs, n = 20, each). Adenocarcinoma cells in the cases with PDPN-positive cases showed significant higher positive ratio for Geminin than in the cases with PDPN-negative CAFs (9.2% vs 2.5%, p < 0.01) (Figure 5C).

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