Fig. 1: Hpa2 attenuates cervical tumor growth.

A Immunostaining. Tissue array of 180 biopsies of cervical squamous cell carcinoma and normal cervical tissue were subjected to immunostaining applying anti-Hpa2 antibody (#58). Shown are representative images of Hpa2 staining in normal cervical tissue (upper left panel; scale bars represent 50 microns) and tumor biopsies stained negative (0; second panels) or positive, exhibiting weak (+1; third panels) or strong (+2; fourth panels) staining intensity of Hpa2. Original magnification: ×10 (left panels; scale bars represent 500 microns), ×100 (right panels; scale bars represent 50 microns). Inset. KM survival analysis. Levels of Hpa2 were retrieved from a large cohort (n = 304) of cervical carcinoma patients, and survival analysis was calculated by a public server (KM plotter service; https://kmplot.com/analysis). Note prolonged survival of cervical carcinoma patients exhibiting high levels of Hpa2; P = 0.002. B Tumor growth. SiHa cervical carcinoma cells were transfected with empty vector (Vo), Hpa2 (WT), or with Pro140Arg (140) and Asn543Ile (543) missense Hpa2 mutants. Following selection, cells were expanded, pooled, and implanted (5 × 10⁶) subcutaneously in NOD/SCID mice. Tumor volume was inspected over time using caliper measurements (upper panel). Upon termination, tumors were collected, weighed (second panel), and photographed (third panel). C Tumor microenvironment. In addition to Hpa2 immuno-reactivity in tumor cells, the staining also revealed that immune cells that comprise the tumor microenvironment are also stained positive for Hpa2. The white arrow points to fibroblast-like cells that appear Hpa2-negative. Original magnification: ×100 (scale bars represent 50 microns).