Malignant progression of a mouse fibrosarcoma by host cells reactive to a foreign body (gelatin sponge)

Abstract

Summary The QR regressor tumour (QR-32), a fibrosarcoma which is unable to grow progressively in normal syngeneic C57BL/6 mice, was able to grow progressively in 13 out of 22 mice (59%) when it was subcutaneously coimplanted with gelatin sponge. We established four culture tumour lines from the resultant tumours (QRsP tumour lines). These QRsP tumour lines were able to grow progressively in mice even in the absence of gelatin sponge. The ability of QRsP tumour cells to colonise the lungs after intravenous injection and to produce high amounts of prostaglandin E2 (PGE2) during in vitro cell culture was much greater than that of parent QR-32 cells. These biological characteristics of QR-32 cells and QRsP tumour cells were found to be stable for at least 6 months when they were maintained in culture.We also observed that QR-32 cells were able to grow progressively in five out of 12 (42%) mice after coimplantation with plastic non-adherent peritoneal cells obtained from mice which had been intraperitoneally implanted with gelatin sponge. These host cells reactive to gelatin sponge increased the production of high amounts of PGE2 by QR-32 cells during 48 h coculture. Preliminary in vitro studies implicated the involvement of hydrogen peroxide and hydroxyl radical as some of the factors necessary to induce QR-32 cells to produce high amounts of PGE2 and to accelerate tumour progression.

Enhancement of in vitro prostaglandin E2 production by mouse fibrosarcoma cells after co-culture with various anti-tumour effector cells

“…We have also observed that PGE2 acts not only as an immunosuppressive factor but also as a positive factor for the chemotactic and motile behaviour of tumour cells (Young et al, 1991). These previous observations revealed that enhanced PGE2 production by tumour cells results in the malignant progression of the tumour cells (Okada et al, 1992). QR-32 cells produce large amounts of PGE2 when the tumour cells have been co-cultured with foreign body-reactive cells (Okada et al, 1992).…”

“…We found that the threshold level of POE2 production necessary to suppress host immune reactivity in vivo is equivalent to approximately 6,000pgml-' of medium in vitro, a value which was produced by 1 x 104 tumour cells during a 48 h culture (Okada et al, 1990(Okada et al, , 1992. Japan).…”

“…These previous observations revealed that enhanced PGE2 production by tumour cells results in the malignant progression of the tumour cells (Okada et al, 1992). QR-32 cells produce large amounts of PGE2 when the tumour cells have been co-cultured with foreign body-reactive cells (Okada et al, 1992). In this study, we therefore attempted to determine which cell type of the anti-tumour effector cells is involved in the induction of QR-32 cell progression.…”

“…We considered that, because PGE2 suppressed the anti-tumour effector cell induction at the site of tumour implantation in the tumorgenic parental BMT-11 cl-9 cells, the regression of QR-32 cells was likely to be due to a decrease in the production of PGE2 (Okada et al, 1990)_ We have also observed that oxygen radicals produced by host cells reactive to foreign bodies such as gelatin sponge augment the production of PGE2 by QR-32 cells during co-culture in vitro. The enhanced production of immunosuppressive PGE2 facilitates the progressive growth of tumours in normal mice when they are given a subcutaneous injection of mixtures of host cells reactive to gelatin sponge and QR-32 cells (Okada et al, 1992). In our mouse tumour model, PGE2 acts not only to augment the in vivo growth of tumour cells but also as a positive factor for the chemotaxis of tumour cells, as well as enhancing QR-32 cell-derived progressor tumour cell migration and dissemination (Young et al, 1991).…”

Cancer cell progression and chemoimmunotherapy-dual effects in the induction of resistance to therapy

“…Since the anti-tumour effects of chemoimmunotherapy with CY and lentinan are T cell dependent (M Suzuki et al, unpublished results), host inflammatory cells may be involved in the tumour disruption process. Recent reports demonstrated that oxygen radicals produced by host inflammatory cells induced the augmentation of PGE2 production by tumour cells and that the enhanced production of PGE2 from tumour cells is closely related to the phenotype changes of tumour cells from benign to malignant (Okada et al, 1990(Okada et al, , 1992(Okada et al, , 1994. The elucidation of exact mechanisms for the increased production of PGE2 during therapy requires further detailed studies.…”