Abstract
Simple SummaryKidney cancer is a common malignant tumor in both men and women and accounts for approximately 5% of all cancer incidences. Advances in imaging technology and the increasing use of health care facilities have led to the early detection of kidney cancer cases. However, many individuals are still diagnosed with metastatic kidney cancer. If the cancer is accompanied by metastases at the time of diagnosis, the 5-year survival rate is 12%. Despite the beneficial effects of anticancer drug treatment on the survival of patients with metastatic kidney cancer, survival may be less than a year. PDLIM2 plays an essential role in cancer formation and inhibition. To verify oncogenic function of the PDLIM2, we conducted several experiments and animal experiments. Our findings indicating that PDLIM2 may be a new therapeutic target for metastatic kidney cancer.We evaluated the expression of PDLIM2 in human kidney cancer cell lines from primary or metastatic origins and found that PDLIM2 expression was highly elevated in metastatic kidney cancers. We evaluated the effect of PDLIM2 inhibition by RNA interference method. PDLIM2 knockdown showed the decreased proliferation and metastatic character in human metastatic kidney cancer cells. By repeated round of orthotopic injection of RenCa mouse kidney cancer cell line, we obtained metastatic prone mouse kidney cancer cell lines. PDLIM2 expression was highly expressed in these metastatic prone cells comparing parental cells. In addition, we evaluated the in vivo efficacy of PDLIM2 knockout on the tumor formation and metastasis of kidney cancer cells using a PDLIM2 knockout mice. The experimental metastasis model with tail vein injection and orthotopic metastasis model injected into kidney all showed reduced lung metastasis cancer formation in PDLIM2 knockout mice comparing control Balb/c mice. Overall, our findings indicate that PDLIM2 is required for cancer formation and metastasis in metastatic kidney cancer, indicating that PDLIM2 may be a new therapeutic target for metastatic kidney cancer.
Highlights
Kidney cancer is a common malignant tumor in both men and women and accounts for approximately 5% of all cancer incidences [1]
Our results indicate that PDLIM2 inhibition can effectively inhibit lung tumor formation in experimental metastasis model of kidney cancer cells xenograft model
After formaldehyde fixation, liver, spleen, and lung tissues from control and PDLIM2 knockout mice were stained with hematoxylin and eosin (H&E), and we found that the size and the number of the cancers in PDLIM2-knockout mice was smaller than that in the control mice (Figure 7D)
Summary
Kidney cancer is a common malignant tumor in both men and women and accounts for approximately 5% of all cancer incidences [1]. The 5-year survival rate of people with kidney cancer is approximately 75%; the survival rate depends on a number of factors, including the histologic subtype, tumor size, and stage of cancer upon first diagnosis. Kidney cancer in about two-thirds of patients “diagnosed at early stages is localized to the kidney and these people have a 5-year survival rate of 93%. If kidney cancer has already spread to surrounding tissues or local lymph nodes at the time of diagnosis, the 5-year survival rate of the patient is 70%. If the cancer is accompanied by distant metastases at the time of diagnosis, the 5-year survival rate is 12% [5]. Despite the beneficial effects of vascular endothelial growth factor inhibitors on the survival of patients with metastatic kidney cancer, survival may be less than a year [5]. Identification of new molecular targets is necessary for the effective treatment of patients with metastatic kidney cancer
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