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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

Engraftment rate and tumor volume of NCI-H82 injected with CAFs in mouse subcutaneous tissue(A) Rate of cancer engraftment at 1, 2, 3, and 4 weeks. (B) Tumor volume of engrafted tumors at 1, 2, 3, and 4 weeks. (C) Histological features of engrafted tumors at 4 weeks after tumor cell injection (H.E. staining) (left, group of CAFs-Ctrl; right, group of CAFs-PDPN).
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Figure 4: Engraftment rate and tumor volume of NCI-H82 injected with CAFs in mouse subcutaneous tissue(A) Rate of cancer engraftment at 1, 2, 3, and 4 weeks. (B) Tumor volume of engrafted tumors at 1, 2, 3, and 4 weeks. (C) Histological features of engrafted tumors at 4 weeks after tumor cell injection (H.E. staining) (left, group of CAFs-Ctrl; right, group of CAFs-PDPN).

Mentions: Next, we examined whether CAFs-PDPN influences tumor engraftment or tumor volume. NCI-H82 cells were subcutaneously co-injected with either CAFs-PDPN or CAFs-Ctrl into SCID mice. The tumor formation rates of NCI-H82 cells co-injected with CAFs-Ctrl and of cells co-injected with CAFs-PDPN were 75% and 63%, respectively at 2 weeks and 88% and 100%, respectively, at 4 weeks (P = 0.59) (Figure 4A). The tumor volume resulting from co-injection with CAFs-Ctrl was larger than the tumor volume resulting from co-injection with CAFs-PDPN at 4 weeks (mean tumor volume: CAFs-PDPN, 757.1 mm3 vs. CAFs-Ctrl, 1469 mm3); however, the difference was not significant (Figure 4B).


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)

Engraftment rate and tumor volume of NCI-H82 injected with CAFs in mouse subcutaneous tissue(A) Rate of cancer engraftment at 1, 2, 3, and 4 weeks. (B) Tumor volume of engrafted tumors at 1, 2, 3, and 4 weeks. (C) Histological features of engrafted tumors at 4 weeks after tumor cell injection (H.E. staining) (left, group of CAFs-Ctrl; right, group of CAFs-PDPN).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Engraftment rate and tumor volume of NCI-H82 injected with CAFs in mouse subcutaneous tissue(A) Rate of cancer engraftment at 1, 2, 3, and 4 weeks. (B) Tumor volume of engrafted tumors at 1, 2, 3, and 4 weeks. (C) Histological features of engrafted tumors at 4 weeks after tumor cell injection (H.E. staining) (left, group of CAFs-Ctrl; right, group of CAFs-PDPN).
Mentions: Next, we examined whether CAFs-PDPN influences tumor engraftment or tumor volume. NCI-H82 cells were subcutaneously co-injected with either CAFs-PDPN or CAFs-Ctrl into SCID mice. The tumor formation rates of NCI-H82 cells co-injected with CAFs-Ctrl and of cells co-injected with CAFs-PDPN were 75% and 63%, respectively at 2 weeks and 88% and 100%, respectively, at 4 weeks (P = 0.59) (Figure 4A). The tumor volume resulting from co-injection with CAFs-Ctrl was larger than the tumor volume resulting from co-injection with CAFs-PDPN at 4 weeks (mean tumor volume: CAFs-PDPN, 757.1 mm3 vs. CAFs-Ctrl, 1469 mm3); however, the difference was not significant (Figure 4B).

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