Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice

Abstract

Summary HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 106 ml-X) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ngml-' within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-1L6 cells were transplanted into C57BL/6 mice subcutaneously, the mean ± s.d. of survival times of these mice were 33.3 ± 9.7, 34.3 ± 7.1 and 17.0 ± 3.1 days, respectively. The survival time of LLC-1L6 cells transplanted mice was significantly shorter than that of LLC (P<0.01) or LLC-Neo (P<0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-1L6 transplanted mice than in LLC transplanted mice. Mouse IL-la and mouse TNF-a were not detected in the plasma of LLC-1L6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-Ia and TNF-a in the plasma. This state may be responsible for the shortened survival of LLC-1L6 tumour-bearing mice.

The relationship between weight loss and interleukin 6 in non-small-cell lung cancer

“…The circulating concentrations of interleukin 6 were consistently higher in the group with at least 5% weight loss compared with the group without weight loss. Recent animal work (Strassman et al, 1992;Ohe et al, 1993) indicates that interleukin 6 has a pivotal role in the development of cancer cachexia. The circulating concentrations of interleukin 6 were consistently higher in the group with at least 5% weight loss compared with the group without weight loss.…”

N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and suppresses neuroblastoma tumor growth

“…Indeed, though in vitro proliferation of IL-6-expressing WAC2 clones was not substantially di erent from that of the parental and control WAC2 clones, their xenograft tumor growth rate was decreased and correlated with a statistically signi®cant reduction in the number of new capillaries. Previous overexpression of IL-6 cDNA in Lewis lung carcinoma cells did not alter the growth rate of syngeneic tumors (Ohe et al, 1993) suggesting that, indeed, IL-6 might play an important role in the balance of angiomodulators in the vicinity of N-myc ampli®ed neuroblastomas.…”

Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect

“…One of these factors, IL-6, is a pleiotropic cytokine physiologically involved in the differentiation of myeloid and neuronal cells, and pathologically involved in the early host response to infection and injury (Kishimoto, 1989), in the proliferation of myeloma (Kawano et al, 1988), urological cancer cells (Miki et al, 1989;Okamoto et al, 1997a,b) and possibly breast cancer cells (Chiu et al, 1996), and in the development of hypercalcaemia and osteolytic metastases (De La Mata et al, 1995). A series of studies have suggested that IL-6 secreted from tumour cells is one of the cachectic factors in animal models of murine colon cancer or of xenograft tumours in athymic nude mice (Greenberg et al, 1992;Strassmann et al, 1992b;Ohe et al, 1993;Fujimoto-Ouchi et al, 1995;Yasumoto et al, 1995;Billingsley et al, 1996;Kajimura et al, 1996;Mori et al, 1996;Ohira et al, 1996;Tsujinaka et al, 1996). Recently, clinical reports have also suggested that elevated IL-6 levels in the sera of patients with oesophageal cancer correlate with their bodyweight loss (Oka et al, 1996), and that a decrease in serum IL-6 levels induced by medroxyprogesterone acetate (MPA) correlates with a reversion of bodyweight loss in patients with advanced breast cancer (Yamashita et al, 1996).…”