Non-erythroid spectrin (fodrin) in cutaneous tumours: diminished in cell membranes, increased in the cytoplasm

Abstract

The expression and distribution of non-erythroid spectrin (alpha-fodrin), a basic protein of the cell membrane skeleton, was investigated by immunohistochemical methods in 42 cutaneous tumours. The suprabasal keratinocytes of the normal epidermis showed plasma membrane-associated spectrin. The basal cells of the normal epidermis, seborrhoeic keratosis, and basal cell carcinoma, revealed both intracytoplasmic and membrane-bound spectrin. In squamous cell carcinoma, the expression of spectrin was heterogeneous and mostly intracytoplasmic. The dysplastic cells of solar keratosis expressed no spectrin at all. In various types of melanocytic naevi, intracytoplasmic and discontinuous membrane-bound spectrin was found in most tumour cells. Malignant melanomas showed a heterogeneous intracytoplasmic staining for spectrin, or were negative. The results indicate a diminished amount, or a total lack, of membrane-bound spectrin with increasing depolarization and proliferation of cells in solar keratosis and pigment cell tumours, but a partial preservation in polarized cells of basal cell carcinoma. The increase and heterogeneity, in cytoplasmic spectrin, of squamous cell carcinoma and malignant melanoma seemed to be associated with the less differentiated, invasive cells of these malignant tumours.

The Role of Nonerythroid SpectrinαII in Cancer

“…Basal as well as squamous cell carcinomas and malignant melanomas display increasing invasion and metastatic capacities, probably reflected by the different patterns of SPTAN1 expression. This supports the concept that the absence or decrease of membrane-associated SPTAN1 is essential for proliferation and increased cytoplasmic SPTAN1 during invasion [39]. In melanomas, however, some cells were strongly stained, while others were completely negative for SPTAN1.…”

“…As already mentioned, SPTAN1 has been mostly shown to be upregulated in tumors compared to normal mucosa (Table 1) [28, 32, 33, 35, 36, 39–41]. In particular, SPTAN1 expression was increased heterogeneously in the cytoplasm, whereas membrane bound SPTAN1 partly disappeared as described in cutaneous tumors [39].…”

“…In cutaneous tumors of various origins, loss of membrane-associated SPTAN1 was detected, whereas cytoplasmic staining of SPTAN1 was increased and associated with less differentiated, invasive cells of these tumors [39]. Basal as well as squamous cell carcinomas and malignant melanomas display increasing invasion and metastatic capacities, probably reflected by the different patterns of SPTAN1 expression.…”

“…Whereas membranous SPTAN1 can act as a cytoskeletal scaffold by interacting with associated proteins and thereby ensures cell polarity, its distribution throughout the cell allows SPTAN1 access to other potential interacting partners and may enhance cell growth and cell proliferation [28]. Therefore, increase of cytoplasmic SPTAN1 was related to the proliferative and invasive capacity of cells and suggested as a marker for neoplasia (Figure 2(b)) [28, 36, 39, 57, 58]. The impact of SPTAN1 on proliferation could be confirmed by in vitro data of our group showing a clear decrease of cell proliferation in SPTAN1-deficient cells [30].…”

Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1

“…Deregulation of spectrins, especially of SPTAN1 seriously affects cellular behavior and promotes tumor progression. Upregulated SPTAN1, e.g., was demonstrated in various types of tumors [20-23] and shown to be associated with local aggressiveness and metastic behavior of soft tissue carcinomas [24]. Moreover, enhanced SPTAN1 was linked to tumor progression and malignancy in ovarian cancer [25] and described to be involved in the carcinogenesis of sporadic CRC [21].…”