Abstract
Activated Leukocyte Cell Adhesion Molecule (ALCAM) has been linked to the progression of numerous human cancers, where it appears to play a complex role. The current study aims to further assess the importance of ALCAM in prostate cancer and the prognostic potential of serum ALCAM as a biomarker for prostate cancer progression. Here we demonstrate enhanced levels of tissue ALCAM are associated with metastasis. Additionally, elevated serum ALCAM is indicative of progression and poorer patient outlook, and demonstrates comparable prognostic ability to PSA in terms of metastasis and prostate cancer survival. ALCAM suppression enhanced proliferation and invasiveness in PC-3 cells and motility/migration in PC-3 and LNCaP cells. ALCAM suppressed PC-3 cells were generally less responsive to HGF and displayed reduced MET transcript expression. Furthermore a recombinant human ALCAM-Fc chimera was able to inhibit LNCaP cell attachment to HECV and hFOB1.19 cells. Taken together, ALCAM appears to be a promising biomarker for prostate cancer progression, with enhanced serum expression associated with poorer prognosis. Suppression of ALCAM appears to impact cell function and cellular responsiveness to certain micro environmental factors.
Highlights
Dissemination and metastatic spread of cancer cells is a key determinant of patient prognosis and the bone is a common site for metastasis arising from prostate cancer [1]
Higher levels of Activated Leukocyte Cell Adhesion Molecule (ALCAM) were observed in patients who died of prostate cancer (PRCa) compared to those who were still alive (Figure 2A, p < 0.001) and in M1 patients compared to M0 patients (Figure 2B, p = 0.002), with borderline significant elevations observed in N1 compared to N0 patients (Figure 2C, p = 0.05)
The current study aimed to further explore the relevance of ALCAM in prostate cancer cells and associated mechanisms, the potential of serum ALCAM to act as a biomarker of prostate cancer and the impact of an ALCAM-Fc chimera, containing extracellular regions of ALCAM, to influence other cell types involved in the metastatic cascade
Summary
Dissemination and metastatic spread of cancer cells is a key determinant of patient prognosis and the bone is a common site for metastasis arising from prostate cancer [1]. ALCAM has been implicated to influence cellular traits associated with cancer progression in vitro and in vivo [6,7,8,9,10,11], though there is some conflict within the literature. Alterations in ALCAM expression have been reported and associated with the progression or prognosis of various human cancers including, breast [7, 12,13,14,15], melanoma www.oncotarget.com [16, 17] and gastric [18, 19] cancer, there are again contrasting reports within the literature
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