Subperitoneal fibroblasts (SPFs) actively contribute to cancer progression.

<p>(A, left) Xenograft tumor growth in mice injected with DLD-1 human colorectal cancer cells alone (blue line, 840.7±112.6 mm³ in 7 weeks), co-injected with DLD-1 cells and submucosal fibroblasts (SMFs; red line, 1178.0±177.6 mm³ in 7 weeks), and co-injected with DLD-1 cells and subperitoneal fibroblasts (SPFs; green line, 1672.8±214.7 mm³ in 7 weeks). The differences of tumor volume between DLD-1 cells alone and DLD-1 cells with SPFs, and between DLD-1 cells alone and DLD-1 cells with SMFs were statistically significant (<i>P</i><0.05). (A, right) Xenograft tumor growth in mice injected with Caco-2 human colorectal cancer cells alone (blue line, 308.6±127.7 mm³ in 9 weeks), co-injected with Caco-2 cells and SMFs (red line, 1363.1±284.3 mm³ in 9 weeks), and co-injected with Caco-2 and SPFs (green line, 2595.1±349.5 mm³ in 9 weeks). The differences of tumor volume between Caco-2 cells alone and Caco-2 cells with SPFs (<i>P</i><0.01), and between Caco-2 cells with SMFs and Caco-2 cells with SPFs (<i>P</i><0.05) were statistically significant. Xenograft tumors derived from co-injection of cancer cells and SPFs grew faster than those derived from injection of cancer cells alone, or co-injection of cancer cells and SMFs. (B, left) Xenograft tumor weight in mice injected with DLD-1 cells alone was 0.71±0.11 g, co-injected with DLD-1 cells and SMFs was 1.27±0.19 g, and co-injected with DLD-1 cells and SPFs was 1.82±0.28 g in 8 weeks. The differences of tumor weight between DLD-1 cells alone and DLD-1 cells with SPFs (<i>P</i><0.01), and between DLD-1 cells alone and DLD-1 cells with SMFs (<i>P</i><0.05) were statistically significant. (B, right) Xenograft tumor weight in mice injected with Caco-2 cells alone was 0.53±0.24 g, co-injected with Caco-2 cells and SMFs was 1.91±0.34 g, and co-injected with Caco-2 cells and SPFs was 3.66±0.45 g in 10 weeks. The differences of tumor weight between DLD-1 cells alone and DLD-1 cells with SPFs (<i>P</i><0.01), between DLD-1 cells alone and DLD-1 cells with SMFs (<i>P</i><0.05), and between DLD-1 cells with SPFs and DLD-1 cells with SMFs (<i>P</i><0.05) were statistically significant. Weights of xenograft tumors derived from co-injection of cancer cells with SPFs were higher than those of tumors derived from injection of cancer cells alone, or co-injection of cancer cells and SMFs (left: DLD-1, right: Caco-2). (C) Although the value did not reach statistical significance, xenograft tumors derived from co-injection of DLD-1 cells and SPFs showed twice the frequency of lymph node metastasis (n = 4) compared to those deriving from co-injection of DLD-1 cells and SMFs (n = 2). (D) Co-injection of cancer cells and SPFs result in enhanced tumor formation capacity. Results are presented as the mean ± SE of 8 mice (*<i>P</i><0.05. **<i>P</i><0.01).