Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces.

Abstract

Osteopontin, a glycoprotein with a glycine-arginine-glycine-aspartate-serine (GRGDS) cell-binding domain, has been described in bone and is also known to be expressed in other organs, particularly kidney. The goal of the present work was to define the distribution of osteopontin synthesis and deposition in a wide variety of normal adult human tissues using a multifaceted approach that included immunohistochemistry, in situ hybridization, and Northern analysis. Immunohistochemical studies have revealed the unexpected finding that osteopontin is deposited as a prominent layer at the luminal surfaces of specific populations of epithelial cells of the gastrointestinal tract, gall bladder, pancreas, urinary and reproductive tracts, lung, breast, salivary glands, and sweat glands. Northern analyses identified gallbladder as a major site of osteopontin gene transcription comparable in magnitude with that of kidney, and immunoblotting identified osteopontin in bile. In situ hybridization localized osteopontin gene transcripts predominantly to the epithelium of a variety of organs as well as to ganglion cells of bowel wall. Osteopontin of epithelial cell origin, like bone-derived osteopontin, promoted GRGDS-dependent cell spreading in attachment assays. We postulate that osteopontin secreted by epithelium binds integrins on luminal surfaces. Collectively, these findings suggest an important role for osteopontin on many luminal epithelial surfaces communicating with the external environment.

Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells

“…Although the secreted phosphoprotein OPN has been shown to be present in increased levels in the primary tumors and plasma of breast cancer patients (Brown et al, 1994;Hirota et al, 1995;BellahceÁ ne and Castronovo, 1995;Senger et al, 1988;Singhal et al, 1997;Tuck et al, 1998), with levels in some instances associated with prognosis (Singhal et al, 1997;Tuck et al, 1998), little is known about whether OPN functionally a ects the malignancy of human breast carcinoma cells, and if so, by what mechanism. We have here undertaken to examine the ability of members of a progression series of breast epithelial cells (21T) (Band et al, 1990) (in comparison with the highly metastatic breast carcinoma cell line MDA-MB-435) to synthesize OPN, and to respond to OPN by increased invasiveness and protease expression.…”

“…Osteopontin (OPN) is a secreted, integrin-binding glycophosphoprotein whose levels are increased in the primary tumors and plasma of patients with breast cancer (Brown et al, 1994;Hirota et al, 1995;BellahceÁ ne and Castronovo, 1995;Senger et al, 1988;Singhal et al, 1997;Tuck et al, 1998). Our clinical studies have shown a relationship between plasma OPN, tumor burden, and prognosis in patients with metastatic breast cancer (Singhal et al, 1997), as well as between tumor cell OPN and prognosis in patients with lymph node negative breast cancer (Tuck et al, 1998).…”

“…Studies have shown that OPN may be synthesized by tumor-in®ltrating macrophages (Brown et al, 1994;Hirota et al, 1995) and by breast cancer cells themselves (Senger et al, 1983;Morris et al, 1993;Bautista et al, 1994;Tuck et al, 1998), although the relative biologic signi®cance of these di erent potential sources of OPN is not yet understood. Previous work (Xuan et al, , 1995Senger and Perruzzi, 1996) has shown that some breast cancer cells show integrin-dependent adhesion to, and migratory response to OPN.…”

Transcriptional regulation of osteopontin gene in vivo by PEBP2αA/CBFA1 and ETS1 in the skeletal tissues

“…The opn gene contains a Gly-Arg-Gly-Asp-Ser (GRGDS) -encoding motif that promotes cell attachment via avb3 integrin (Oldberg et al, 1986) and CD44 (Weber et al, 1996). Opn has been suggested to play important roles in the process of neoplastic metastasis (Brown et al, 1994;Oates et al, 1996) by enhancement of cell attachment through Opn receptors. In addition to the integrin binding consensus sequence, Opn contains several additional putative functional domains; a stretch of nine or ten aspartic acid residues that could play a role in hydroxyapatite binding, two heparin binding domains, and a calcium binding domain (Denhardt and Guo, 1993).…”

Expression of Osteopontin in oesophageal squamous cell carcinoma

“…Other molecules which share this domain include fibronectin, vitronectin and a variety of other extracellular proteins that bind members of the integrin family of cell surface receptors (Varner and Cheresh, 1996). The expression of Osteopontin has subsequently been demonstrated in a wide range of normal human tissue and body fluid such as osteoblasts, arterial smooth muscle cells, leukocytes, activated macrophages and T cells (Coppola et al, 2004), and epithelia of the gastro-intestinal tract (Brown et al, 1992;Brown et al, 1994). It is a multifunctional protein involved in cell adhesion and cell migration, and has been shown to play important roles in tumorigenesis, tumour invasion, metastasis and prognosis among patients with breast (Tuck et al, 1998), lung (Zhang et al, 2001;Donati et al, 2005), prostate (Thalmann et al, 1999), gastric (Ue et al, 1998) and colon cancer (Agrawal et al, 2002).…”