The Onco-Embryonic Antigen ROR1 Is Expressed by a Variety of Human Cancers

Abstract

ROR1 is an orphan-receptor tyrosine-kinase-like surface antigen that is expressed by many tissues during embryogenesis, some B-cell malignancies, and various cancer cell lines but not by virtually all normal adult tissues. Here, we report that large proportions of many different human cancers also express ROR1, particularly those cancers that have high-grade histology. Primary cancers that expressed ROR1 more commonly expressed high levels of phosphorylated AKT (p-AKT) and phosphorylated cAMP response element binding-factor (p-CREB) than similar cancers that lacked expression of ROR1. Induced expression of ROR1 could enhance basal p-AKT and p-CREB levels and could promote the growth of a cancer cell line, MEC1. Conversely, silencing ROR1 resulted in lower levels of p-AKT and p-CREB, which was associated with impaired tumor cell growth. In summary, this study found that many different human cancers express ROR1 and that ROR1 may play a functional role in promoting tumor cell growth, suggesting that this orphan-receptor tyrosine-kinase-like protein may be a potential target for therapy directed against a variety of human cancers.

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

“…Moreover, cases of ovarian cancer that had low malignant potential generally had low-to-negligible expression of ROR1. Consistent with these observations, we noted that ovarian cancers that expressed ROR1 by immunohistochemistry more commonly had a high-grade, less-differentiated histology (30), which typically is associated with aggressive disease (41). This also is consistent with a recently published study indicating that high-level expression of ROR1, assessed by immunohistochemistry of primary tumor tissue, was an independent prognostic factor for predicting relatively short diseasefree survival or overall survival of patients with ovarian cancer (34).…”

“…Prior studies found that expression of ROR1 could enhance tumor-cell proliferation, migration/invasion, and tumorigenicity (30,33,40). Conversely, silencing ROR1, or treatment with an anti-ROR1 mAb, could enhance apoptosis, inhibit cell proliferation and migration/invasion, and reduce the capacity of tumor cells to develop metastatic foci (30,31,33).…”

“…Conversely, silencing ROR1, or treatment with an anti-ROR1 mAb, could enhance apoptosis, inhibit cell proliferation and migration/invasion, and reduce the capacity of tumor cells to develop metastatic foci (30,31,33). Similarly, silencing ROR1 could inhibit the capacity of primary ovarian cancer cells to form spheroids, invade ECM, or to develop tumor xenografts, which are functional characteristics associated with CSCs.…”

“…ROR1 is a type I orphan-receptor tyrosine kinase-like surface protein that is found on neoplastic cells of many different types of cancer, but not on normal adult tissues (26)(27)(28)(29)(30)(31)(32). Moreover, ROR1 predominately seems to be expressed by less well-differentiated tumors that have high potential for relapse and metastases and that also express markers associated with EMT (31,33).…”

Investigating the Molecular Specific Interactions on Cell Surface Using Atomic Force Microscopy

“…In order to investigate the CD20 on cancer B cells, we need to recognize cancer B cells first. Recent research work indicate that receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a specific cell surface marker expressed on some B-cell lymphomas (such as mantle cell lymphoma, marginal zone lymphoma, diffuse B-cell lymphoma, and follicular lymphoma) but not on virtually all normal adult tissues [47,48]. Hence, ROR1 is a suitable marker for distinguishing tumor B cells from healthy cells.…”