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Changes in insulin receptors on methylcholanthrene-induced sarcoma during growth
1Division of Oncologic Surgery, City of Hope National Medical Center, Duarte, California 91010.
Abstract:
Methylcholanthrene-induced sarcomas (MCA-S) have different growth patterns in diabetic (D) and nondiabetic (ND) rats. Diabetes delays the early phase of tumor growth and prolongs survival. This study evaluated MCA-S growth and its relation to insulin receptors (IR) and glucose uptake. Fisher 344 rats 150-200 g were assigned to two groups: Diabetic tumor bearers (DTB, n = 26) and nondiabetic tumor bearers (NDTB, n = 18). Diabetes was induced with iv streptozocin (40 mg/kg); MCA-S was inoculated (1 X 10(6) cells) subcutaneously 10 days later. Animals were sacrificed during early growth (tumor volume less than or equal to 20 cc) or logarithmic growth (tumor volume greater than 20 cc). IR assay was performed (0-10(5) ng/ml cold insulin, 25 X 10(3) cpm/tube A14 125I-insulin, 90 min, 15 degrees C, pH 7.8) on a single cell preparation. Serum glucose milligrams per deciliter and insulin nanograms per milliliter were assayed. Glucose uptake (dpm/g tissue/hr) was assayed 2 hr after an ip injection of 0.5 microCi 3-O[14C]methylglucose. Diabetic, tumor-bearing animals had a significantly increased number of insulin receptors at the small [less than or equal to 20 cc, 28.7 (D) vs 8.3 (ND)] and large [greater than 20 cc, 82.8 (D) vs 27.8 (ND)] tumor volumes. Glucose uptake was increased in the tumor at both volumes in the non-diabetic animals compared to the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Diabetes significantly increases insulin receptors in methylcholanthrene-induced sarcomas (MCA-S) but decreases glucose uptake in tumor cells. This impacts tumor growth and survival in diabetic rats.
Area of Science:
- Oncology
- Endocrinology
- Metabolism
Background:
- Methylcholanthrene-induced sarcomas (MCA-S) exhibit distinct growth dynamics in diabetic versus nondiabetic rats.
- Diabetes mellitus is known to influence tumor progression and host survival.
- Understanding the interplay between diabetes, tumor biology, and metabolic pathways is crucial.
Purpose of the Study:
- To investigate the relationship between methylcholanthrene-induced sarcoma growth, insulin receptor (IR) expression, and glucose uptake in diabetic and nondiabetic rats.
- To elucidate the impact of diabetes on the molecular mechanisms governing tumor growth.
Main Methods:
- Fisher 344 rats were induced with diabetes using streptozocin and inoculated with MCA-S cells.
- Tumor-bearing animals were categorized into diabetic (DTB) and nondiabetic (NDTB) groups.
- Insulin receptor assays, serum glucose and insulin measurements, and 3-O-[14C]methylglucose uptake studies were performed on tumor tissues at different growth stages.
Main Results:
- Diabetic tumor-bearing animals demonstrated a significantly higher number of insulin receptors in both early (≤20 cc) and advanced (>20 cc) tumor stages compared to nondiabetic controls.
- Conversely, glucose uptake within the tumor tissue was significantly higher in nondiabetic animals compared to diabetic animals across both tumor volume categories.
- Diabetes was observed to delay early tumor growth and prolong host survival.
Conclusions:
- The increased insulin receptor expression in diabetic rat sarcomas suggests a potential compensatory mechanism or altered signaling pathway.
- Reduced glucose uptake in diabetic tumors, despite increased IR, indicates a complex metabolic dysregulation.
- These findings highlight the significant impact of diabetes on sarcoma biology, affecting both tumor growth and host response.