Progression of a Weakly Tumorigenic Mouse Fibrosarcoma at the Site of Early Phase of Inflammation Caused by Plastic Plates

Abstract

To elucidate tumor progression‐enhancing factor(s), we examined the effects of host inflammation and host immunological status on in vivo tumor progression. One × 104 cells of QR clones (QR‐32, ‐20 and ‐18), regressor tumor clones of 3‐methylcholanthrene‐induced fibrosarcoma, were unable to grow when injected s.c. into C57BL/6 mice in cell suspension form. However, QR clones grew and were lethal when s.c. implanted, attached to plastic plates. Furthermore, the tumor lines (QRpP) obtained from the tumors which had arisen from the plate‐attached QR‐32 clone cells no longer required plastic plates for their growth in normal mice, and had acquired stable malignant phenotypes. Although QR‐32 cells became lethal when injected at the site of plastic plate implantation 1, 5 and 10 days before tumor injection, few tumors developed when plastic plates had been implanted 20 or 30 days before tumor injection. We established culture clones from the tumors arising in normal mice and mice immunosuppressed by irradiation. Clones derived from the tumors which had arisen in normal mice after implantation with plastic plates were lethal when re‐implanted in normal mice (71%). On the other hand, clones derived from the tumors that arose in irradiated mice with or without plastic plates were lethal in only a few normal mice, when re‐implanted (20 and 8%, respectively). These results indicate that QR clone cell progression is enhanced by the early phase of inflammation at the site of plastic plate implantation and that the progression‐enhancing activity of co‐implantation with a plastic plate is inhibited by previous whole‐body irradiation of hosts.

Conversion of Human Colonic Adenoma Cells to Adenocarcinoma Cells Through Inflammation in Nude Mice

“…Establishment of the model is based on our previous studies. We earlier established rodent tumor progression models by using poorly tumorigenic or weakly metastatic tumors in normal syngeneic hosts coimplanted with a plastic plate or gelatin sponge Okada et al, 1992Okada et al, , 1993Okada et al, , 1999. Regressive mouse fibrosarcoma cells were converted to more malignant cells after contacting inflammatory cells caused by the plastic plate (Okada et al, 1993) or gelatin sponge in the early phase.…”

“…We have previously found that foreign bodyinduced inflammation not only promotes the local growth of rodent tumors but also converts them into more aggressive tumors; that is, they acquire enhanced tumorigenicity and metastatic ability Okada et al, 1992Okada et al, , 1993. We have reported that inflammation-derived active oxygen species and cytokine/growth factors played major roles in the tumor progression Okada et al, 1992Okada et al, , 1994Okada et al, , 1999.…”

Beyond foreign‐body‐induced carcinogenesis: Impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression

“…88 By using those foreign bodies, we modulated the quality and duration of the inflammation, and found that the type of inflammation needed for QR cells' growth and progression was acute-phase inflammatory reaction. 87,88,94 By histological examination, we found that neutrophils predominantly infiltrated the sponge. 93,94 In fact, one of the benefits of using gelatin sponge is that it is possible to collect the infiltrated inflammatory cells by treating the sponge with collagenase; the inflamed cells separated from the sponge can convert QR cells into tumorigenic ones if both cells are mixed and injected.…”

“…86 QR cells did not form tumors or metastasis after subcutaneous (2 3 10 5 cells) or intravenous (1 3 10 6 cells) injection into mice. 80 However, implantation of 1 3 10 5 QR cells attached to plastic plate 87 or injection into the preinserted gelatin sponge 88 in subcutaneous space of mice induced lethal tumors. Moreover, the arising tumor exhibited metastatic properties.…”

“…88,94 Namely, our primary observation was that foreign-body-reactive, early-phase inflammatory cells contribute to augment malignancy of QR cells. 87,88,94 To test the role of neutrophils during inflammation, we eliminated neutrophils by administering anti-neutrophils antibody (RB6). Nearly all the arising tumors in the mice, nontreated or treated with control rat IgG, acquired malignant phenotypes.…”